African American Prostate Cancer Research Articles

Abstract B052: Exploring supplement utilization patterns among African American prostate and breast cancer survivors

Abstract Introduction: The American Cancer Society (ACS) defines dietary supplements as “vitamins and minerals, herbs and other botanicals, amino acids, enzymes, and more.” ACS advises against supplement use for cancer prevention, with no suggestions for survivors. Regardless, 64-81% of cancer survivors and 14-32% of recently diagnosed cancer patients in the U.S. will begin taking supplements to improve health outcomes. Despite this prevalence, few studies have examined supplement use in African American cancer survivors, and studies that have been done include small samples. This project examines supplement use across two genders and two cancer types within a population group historically underrepresented in research. Given the dearth of research to date, this project adds novel findings to the literature and informs future research.Objectives: This study describes supplement use in African American breast and prostate cancer survivors engaged in lifestyle intervention trials, identifies potential correlates of supplement use; and compares supplement use between the two populations. Methods: Men Moving Forward (MMF) is an ongoing lifestyle intervention study for African American prostate cancer survivors. Moving Forward (MF) is a completed lifestyle intervention study that included African American breast cancer survivors. Both studies examine the efficacy of a community-based intervention that promotes adherence to the American Cancer Society Nutrition and Physical Activity Guidelines. At baseline, study participants completed interviews that included a measure of supplement use including type, dose, frequency, and reason for use. Supplements were then categorized by type (e.g., Vitamin D, Vitamin B12) and descriptive analyses were conducted to examine most common types of supplements used, potential correlates of use, and to compare the two cancer survivor groups. Results: 114 men currently enrolled in the MMF study, and 223 women enrolled in MF completed the supplement use measure. Average ages of participants are 66.2 years (SD=7.5) for MMF and 57.5 years (SD=10.1) for MF. Supplement use was common, with 64.0% of MMF participants and 65.9% of MF participants using at least one supplement at baseline. Mean number of supplements was 1.62 (SD=1.9) for MMF and 1.76 (SD=2.0) for MF. The most used supplements were the same across survivor groups: Vitamin D (37.7% MMF, 38.1% MF), Multivitamins (27.2% MMF, 32.7% MF) and Omega-3 Fatty Acids (8.8% MMF, 19.3% MF). Age, education, and income will be explored as predictors of usage. Conclusions: Supplement use was prevalent among both survivor groups, consistent with national data for adult cancer survivors who report supplement use. However, our sample had higher usage rates compared to Non-Hispanic Black US adults without cancer (39.3% of men, 56.2% of women) from the 2023 National Health Statistics Report. Understanding supplement use in cancer survivors can identify potential risks and benefits of use, enhance patient-provider communication, and improve the quality-of-care patients receive. Citation Format: Carlene Kranjac, Estefania Alonso, Margaret Tovar, Sandra Contreras, Iwalola Awoyinka, Patricia Sheean, Melinda Stolley. Exploring supplement utilization patterns among African American prostate and breast cancer survivors [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B052.

Abstract B068: Physical function and fitness of African American prostate cancer survivors at baseline of Men Moving Forward, a lifestyle intervention program

Abstract Background: Prostate cancer (PC) is the most commonly diagnosed cancer in American men with 1 in 8 men diagnosed in their lifetime. African American men have the highest rates of incidence and mortality for PC in the USA, due to a myriad of socio-biological factors. Fortunately, given advances in screening and treatment options the survival rate of PC is high with a 97% 5-year survival rate. However, PC treatments can cause muscle atrophy and reduced physical functioning and quality of life (QoL). Physical function and strength can serve as proxy measurements for cellular aging, longevity, and QoL. Handgrip is related to overall strength, upper limb function, bone mineral density, and mortality. Sit-to-stand measures leg strength and endurance and is used to evaluate fall risk. The 6-minute walk test (6MW) is used to assess aerobic capacity. Men Moving Forward (MMF) is one of the first community-based lifestyle programs developed with and for African American Prostate Cancer Survivors (AAPCS). This study examines objective and subjective physical function of MMF participants at baseline. Methods: MMF is a randomized, wait-list control trial with a 16-week group-based lifestyle intervention focused on physical activity, nutrition and QoL, led by local health coaches. Participants complete physical assessments and surveys at baseline, post-intervention and 12 months. Physical assessments consist of a blood draw, DXA scan, anthropometric measurements, handgrip strength, 30-second sit-to-stand, and 6MW (added with second cohort). Participants also answer surveys on their health and physical function. Pearson’s correlation was used to assess linear correlation between fitness measures and self-reported physical function. Results: At baseline, 100 AAPCS completed both the physical assessment and survey. Participants had a mean age of 65.8 ± 7.26 years, 49% were married/living with a partner, 47.6% were retired, and education levels varied. Top comorbidities include hypertension, obesity, diabetes, and hypercholesterolemia. Mean hand grip scores were 39.8 ± 7.5kg for right and 38.4 ± 7.7kg for left. Handgrip scores 28.2-44.0kg for men aged 64-69 are considered normal. Mean sit-to-stand (n=96) was 12.2 ± 4.3 reps in 30 seconds. Since 6MW was added later in the study, 68 men completed with a mean score of 0.42 ± 0.10 km. Normal ranges for men aged 65-69 is 15 reps for sit-to-stand and 0.572km for 6MW. 50% of participants rated their overall health as “good”, 21% as “very good”, and 20% as “fair” on a five-point Likert scale. PROMIS physical function measures had an average of 50.3 ± 7.3 for men at baseline. PROMIS physical function was weakly correlated with 6MW and sit-to-stand with r = 0.34, p-value=0.004 and r = 0.27, p- value=0.009, respectively. Conclusion: Data reflect the value of supporting AAPCS in lifestyle changes to improve physical function. Few efforts have addressed lifestyle among AAPCS, despite high prostate cancer burden. Future reports will examine the efficacy of MMF in improving physical function, overall health, and QoL. Citation Format: Margaret Y. Tovar, Iwalola Awoyinka, Patricia Sheean, Paula Papanek, Toni Uhrich, Sandra Contreras, Meheret Gebreegziabher, Estefania Alonso, Jayme Ewens, Shannon Reed, Diana Navarro Suarez, Kathleen O'Connell, Kathryn Flynn, Kathryn Bylow, Deepak Kilari, Melinda Stolley. Physical function and fitness of African American prostate cancer survivors at baseline of Men Moving Forward, a lifestyle intervention program [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B068.

Abstract B062: Physical Activity in African American Prostate Cancer Survivors and a Comparison of Self-report versus Accelerometer-Derived Measurement

Abstract Authors: Shannon Reed, Margaret Tovar, MPH, Paula Papanek, PhD, Patricia Sheean, Deepak Kilari, MD, Katie Bylow, MD, PhD, Whitney Morelli, PhD, Melinda Stolley, PhD Background: The Men Moving Forward intervention examines a lifestyle intervention's effects on body composition among Black/African American prostate cancer survivors (AAPCS). AAPCS. To assess PA, self-report and objective measures are being used. Studies use self-report measurements due to their simplicity and low cost, however, the congruent validity of self-report PA is often questioned. This study describes PA and strength training and also compares self- report PA to accelerometry-derived PA among AAPCS at baseline. Methods: AA men with non-metastatic PC were recruited to participate in a randomized, waitlist control trial testing the efficacy of a lifestyle intervention. The 16-week group and community-based intervention was developed with and for AAPCS and is grounded in the ACS Nutrition and Physical Activity Guidelines for Cancer Survivors. Participants completed the Godin Leisure Time Physical Activity Questionnaire (GLTPAQ) which queries about moderate and vigorous activities. The study added a question about the frequency of strength training. Participants also wore a GT3X accelerometer (Actigraph) for 7 days. Only men who wore the actigraph for at least 10 hours across 4 days were included in this analysis. Troiano 2008 cut points were used to measure moderate-vigorous PA (MVPA). Pearson’s correlation was used to assess linear correlation between objectively measured and self-reported MVPA. Statistical significance was set at p<0.05. Results: 73 AAPCS with a mean age of 65.8 years ± 6.9 were included in the analyses. Mean Godin score was 23.32 +16.80 (insufficient activity) with 45.2% classified as active (Godin score >24) and 54.8% as insufficiently active (Godin score<23). 30.2% strength trained at least twice weekly. Actigraph data showed a mean of 101.19 minutes per day of MVPA and that 73.68% of participants did not meet the guideline for 150 minutes per week of MVPA. The analysis revealed a weak positive correlation (r = 0.274, p = 0.019) between actigraph-recorded MVPA and self-reported MVPA. Conclusion: Study results suggest AAPCS overestimate their MVPA using the GLTPAQ when compared to accelerometry. Notably, a significant proportion did not meet the recommended level of physical activity. These findings underscore the importance of including objective measures of PA and the value of programming that is intentionally inclusive of AAPCS. To better support validity and reliability, participant perceptions of PA time and intensity may require improved clarification and description in studies relying solely on SR questionnaires. Citation Format: Shannon Reed, Margaret Tovar, Paula Papanek, Patricia Sheean, Deepak Kilari, Whitney Morelli, Katie Bylow, Melinda Stolley. Physical Activity in African American Prostate Cancer Survivors and a Comparison of Self-report versus Accelerometer-Derived Measurement [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B062.

Abstract A088: Examining associations between objective and perceived stress and allostatic load in African American prostate cancer survivors

Abstract Background. Racial disparities in prostate cancer survivorship persist despite clinical advancements. Stress has been implicated as a potential driver of these disparities, with both chronic and perceived stress found to be associated with adverse cancer survivorship. Allostatic load (AL), one such marker of chronic stress, has been associated with decreased survivorship and worse quality of life (QoL) in cancer survivors. Perceived stress has also been associated with outcomes in cancer survivorship including increased symptom burden and worse quality of life. Despite this, few studies incorporate direct measures of stress or examine how these measures contribute to AL This study examines the relationship between AL, objective stress (as measured by occurrence of stressful life events), and self-reported perceived stress in a subset of African American prostate cancer survivors (N=59) enrolled in Men Moving Forward, a randomized trial to improve body composition through lifestyle change. Methods. At baseline, participants completed an adapted version of the Crisis in the Family Systems (CRISYS) survey, an instrument designed to measure recent (past 4 months) contemporary life stressors. The survey was tailored for AAPCS via feedback from the community advisory board. 41 items reflective of 11 domains were included. Overall CRISYS scores and scores by domain were calculated. Feelings of perceived stress in the past month were measured via the 10-item perceived stress scale, with higher scores reflecting higher perceived stress. AL scores used 15 criterion reflecting neuroendocrine, cardiovascular, immune, and metabolic systems. Each criterion was assigned a score of 0 or 1: 1 if in the high-risk range based on clinical guidelines. An index score was generated by summing high-risk indicators. Pearson correlations were used to explore the relationship between stress measures. Logistic regression comparing the those with highest quartile AL to lower AL was also performed. Results. The mean AL score was 5.6 (SD ± 2.4) of a maximum score of 15. The mean summative score for CRISYS was 4.8 (SD ± 3.3). The most common domains of stress experienced were safety in the community (67%), relationships (66%), and medical issues of loved ones (44%). The Mean PSS was 11.5 (SD ± 6.0), with 64% of men reporting low stress and 36% moderate stress levels. Significant correlations were found between CRISYS and PSS, however no correlations with AL were detected. No significant findings were identified in the regression analysis. Conclusions. Objective and perceived stress measures were correlated, but no associations were found between the perceived or objective stress measure and AL in this sample.. Given AL is meant to reflect the physiological impact of cumulative and chronic stress burdens, it is possible that the shorter-term context of the objective (past 4 months) and perceived stress (past month) measures were not sufficiently aligned with the longer-term context of AL. Citation Format: Iwalola Awoyinka, Deepak Kilari, Kathryn Bylow, Jennifer Knight, Alexis Visotcky, Anjishnu Banerjee, Patricia Sheean, Paula Papanek, Melinda Stolley. Examining associations between objective and perceived stress and allostatic load in African American prostate cancer survivors [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A088.

Abstract C097: PVT1 exon 9-dependent overexpression of RSAD2 is a characteristic of prostate cancer in males of African ancestry

Abstract Aggressive prostate cancer (PCa), including castrate-resistant and neuroendocrine subtypes, is projected to increase in incidence 5% each year. Aggressive PCa disproportionally impacts African American men, has limited effective treatment options and high mortality rates. Although racial disparities are established in PCa development, attributed to multiple contributory factors including systemic racism, differences in socioeconomic status and distrust in the medical system, work is still needed to understand the contribution of biological factors. We found the exon 9 region of plasmacytoma variant translocation 1 (PVT1) overexpressed in aggressive PCa cell lines derived from African American (AA) men. We found PVT1 exon 9 overexpression induced phenotypic changes to normal prostate epithelial cells in vitro and led to tumor formation in vivo. RNA-sequencing analysis revealed 156 significantly differentially expressed genes influenced by PVT1 exon 9 overexpression and radical S-adenosyl methionine domain containing 2 (RSAD2) was the top significantly overexpressed gene (log2Fold change 1.71, p-value < 0.05). We utilized the GSE223405 publicly available dataset to identify whether our identified PVT1 exon 9 downstream genes were enriched in AA prostate cancer cells. RSAD2 was significantly overexpressed in AA prostate cancer cells compared to prostate cancer cells from men of European ancestry (moEA) (log2Fold change 6.18, p-value < 0.05). Comparing normal cells to prostate cancer cells between these groups, we found that normal AA prostate cells had significantly higher expression of RSAD2 (log2fold change 4.25, p-value < 0.001) whereas moEA samples did not (log2fold change 0.837, p-value=0.150). From analysis of data obtained from cBioPortal, we found RSAD2 alteration significantly correlates (p-value < 0.001) with self-identified race and copy number overexpression of RSAD2 was found to be enriched in AA patients (18.16% moEA versus 24% AA). Finally, we found 88.6% of the significantly differentially expressed genes within our PVT1 exon 9 RNA-sequencing dataset were significantly differentially expressed in GSE223405 AA samples and of those, 51.7% of genes exhibited a similar differential expression pattern suggesting that the PVT1 exon 9/RSAD2 dependent pathway may be more prominent in AA men. Mechanistically, we found two differing pathways of RSAD2 overexpression in aggressive prostate cancer cell models, one dependent and one independent of PVT1 exon 9 overexpression, with similar but differing biological functions related to epigenetic processes and metabolism. Ongoing work is investigating the RSAD2 and PVT1 exon 9 expression axis in a diverse set of human prostate cancer tissues and investigating their utilization as a therapeutic target in prostate cancer. Citation Format: Rachel E. Sexton-Bonacci1, Murtaza Barkarar1, Chindeum Udekwu1, Olorunseun O. Ogunwobi1. PVT1 exon 9-dependent overexpression of RSAD2 is a characteristic of prostate cancer in males of African ancestry [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C097.

Abstract C098: CYR61 expression in prostate cancer patients at City of Hope

Abstract In the US, African-American (AA) and Hispanic/Latino (H/L) men have higher rates of advanced prostate cancer (PCa), increased PCa-specific mortality, and are more likely to undergo metastasis than non-Hispanic White (NHW) men attributed to a lack of access to early screening, and a higher prevalence of risk factors such as obesity, diet, and genetic differences. Consequently, effective treatment of advanced PCa and elimination of racial and ethnic disparities for this malignancy require the identification of mechanisms of disease progression. In PCa, the cysteine-rich angiogenic inducer 61 (CYR61) contributes to malignant cell growth through interactions with extracellular ligands, such as integrins avb3 and a6b4. In previous studies, we have found that CYR61 is upregulated in metastatic PCa cell lines and knockdown of this protein significantly reduced metastatic cell proliferation, viability, prostasphere formation, and activation of the PI3/AKT pathway, indicating a potential utilization of CYR61 inhibition in the therapy of metastatic PCa. Interestingly, we have observed that in metastatic PCa cell models, IGF1 induction increased CYR61 protein expression. However, the correlation between PCa aggressiveness and levels of CYR61 in tumor-derived tissues from patients is poorly studied. Our goal with this study is to identify possible correlations in CYR61 expression that may reflect health disparities in PCa outcomes. We used in silico analyses from whole exome paired tumor/normal DNA sequencing and tumor RNA sequencing data available on 542 PCa cases in the City of Hope POSEIDON database to determine whether gene expression of CYR61 and IGF1 was correlated with genetic ancestry, Gleason score, and tumor purity. In univariate analyses, we found that H/L PCa cases had significantly higher levels of expression of CYR61 than NHW PCa cases (p = 0.043) and that both H/L and AA PCa cases had higher IGF1 expression levels, although only significant in AA (p=0.031). We also found that PCa patients with Gleason scores of 8 and higher had significantly lower expression of IGF1 than those with Gleason scores of 7 or less (p=0.006). Both CYR61 and IGF1 expression levels were significantly lower in those with luminal B (p=0.00000000053, p=0.000009, respectively) and with basal subtypes (p=0.00035, p=0.000069, respectively compared to luminal A subtype. Tumor purity was estimated by RNA-seq based on 141 genes specific to stroma and 141 genes specific to immune cells. CYR61 expression was significantly correlated with stromal and immune infiltration. These results suggest that reduced CYR61 expression is associated with more aggressive PCa. Additional analyses are ongoing to understand the interplay of variables of race and ethnicity, age, Gleason score, and tumor purity and to investigate outcomes of biochemical recurrence and death from PCa. Citation Format: Greisha L. Ortiz-Hernandez, Yuan Chun Ding, Susan L. Neuhausen. CYR61 expression in prostate cancer patients at City of Hope [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C098.

Vitamin K3 derivative inhibits androgen receptor signaling in targeting aggressive prostate cancer cells.

Prostate cancer (PCa) is the second critical cause of cancer-related deaths, with African Americans dying at higher rates in the U.S. The main reasons for the higher mortality rate are ethnic differences and lack of understanding of prostate cancer biology and affordable treatments, as well as the financial burden of African American men to obtain the most effective and safe treatments. The effect of micronutrients, including Vitamin K, on various cancer cell lines has been widely studied, but the potential anticancer effect of VK3-OCH3, an analog of vitamin K3 (Menadione), on African American prostate cancer has not been evaluated. In this study, we compared the anticancer effect of VK3-OCH3 on targeting African American derived PCa cell lines namely RC77-T and MDA-PCa-2b. Our results show that VK3-OCH3 significantly inhibits the proliferation of both RC77-T and MDA-PCa-2b African American PCa cells and promotes apoptosis, and the underlying mechanism of cell death appears to be similar in both the cell lines. Notably, VK3-OCH3 inhibits colony-forming ability and induces apoptosis by blocking the cell cycle at G0 in African American PCa cells. VK3-OCH3 also acts as an anti-metastatic agent by inhibiting the migration ability of the metastatic properties of African American PCa cells. The cell death of African American PCa cells mediated by VK3-OCH3 is associated with the production of free radicals, such as intracellular and mitochondrial reactive oxygen species (ROS). Interestingly, antioxidants such as N-Acetylcysteine (NAC) and Glutathione (GSH) effectively negated the oxidative stress induced by VK3-OCH3 on PCa cell lines derived from African American patients. Of note, VK3-OCH3 reduces androgen receptor and prostate-specific antigen expression in these PCa cells. Furthermore, molecular dynamic studies reiterated that VK3-OCH3 strongly binds to the androgen receptor, suggesting that the androgen receptor is the potential molecular target of VK3-OCH3. In addition, Western blot analysis showed that VK3-OCH3 reduces the expression of androgen receptor, TRX2, and anti-apoptotic signaling molecules such as Bcl-2 and TCTP in the MDA-PCa-2b metastatic PCa cellular model. In conclusion, our results suggested that VK3-OCH3 is a promising anticancer agent that could potentially reduce the mortality rates of African American PCa patients, warranting further preclinical and translational studies.

Combination of miR-99b-5p and Enzalutamide or Abiraterone Synergizes the Suppression of EMT-Mediated Metastasis in Prostate Cancer.

Prostate cancer (PCa) is the most frequently diagnosed cancer and second leading cause of cancer deaths among American men. Androgen deprivation therapy (ADT) has been systemically applied as a first-line therapy for PCa patients. Despite the initial responses, the majority of patients under ADT eventually experienced tumor progression to castration-resistant prostate cancer (CRPC), further leading to tumor metastasis to distant organs. Therefore, identifying the key molecular mechanisms underlying PCa progression remains crucial for the development of novel therapies for metastatic PCa. Previously, we identified that tumor-suppressive miR-99b-5p is frequently downregulated in aggressive African American (AA) PCa and European American (EA) CRPC, leading to upregulation of mTOR, androgen receptor (AR), and HIF-1α signaling. Given the fact that mTOR and HIF-1α signaling are critical upstream pathways that trigger the activation of epithelial-mesenchymal transition (EMT), we hypothesized that miR-99b-5p may play a critical functional role in regulating EMT-mediated PCa metastasis. To test this hypothesis, a series of cell biology, biochemical, and in vitro functional assays (wound healing, transwell migration, cell/ECM adhesion, and capillary-like tube formation assays) were performed to examine the effects of miR-99b-5p mimic on regulating EMT-mediated PCa metastasis processes. Our results have demonstrated that miR-99b-5p simultaneously targets MTOR and AR signaling, leading to upregulation of E-cadherin, downregulation of Snail/N-cadherin/Vimentin, and suppression of EMT-mediated PCa metastasis. MiR-99b-5p alone and in combination with enzalutamide or abiraterone significantly inhibits the EMT-mediated metastasis of AA PCa and EA CRPC.

Abstract 2146: Race-related differential immunoreactivity of enolase autoantibodies in patients with prostate cancer

Abstract INTRODUCTION AND OBJECTIVE: Enolase-1 (ENO1) and -2 (ENO2) are implicated in tumor metabolic and aggressive functions. Like prostate specific membrane antigen (PSMA), they localize to the tumor cell surface and are potential theranostics targets. ENO autoantibodies were reported by our group in prostate cancer (PCa) patients but their immunoreactivity to ENO1/2 isoforms was not defined. Differential ENO immunoreactivity in docetaxel-resistant (DR) PCa cells between African American (AA) and European American (EA) PCa patients was also reported. Our objective was to investigate the role of ENO isoforms in the race-related differential ENO immunoreactivity of PCa patients. METHODS: PCa patient sera (41 AA, 68 EA) were obtained from Loma Linda University Biospecimen Laboratory. Western blotting (WB) analysis, using patient sera and monoclonal antibodies to ENO1 and ENO2, was done against lysates from docetaxel-sensitive (DS) and DR PCa cell lines and against recombinant (rec) ENO1 and ENO2 to assess ENO isoform expression and detect ENO autoantibodies. Scratch-wound assay was performed to evaluate AA and EA anti-ENO driven inhibition of DR PCa cell migration. Student’s T-test and Chi-squared analyses were performed with p<0.05 deemed significant. RESULTS: ENO1 expression was robust in all assessed DS and DR cell lines. ENO2 was detected in DS cells but was significantly reduced in DR cells. PSMA expression was lost in cells expressing ENO1 and neuroendocrine markers. Anti-ENO EA sera reacted in WB with the expected 50 kD band in both DS and DR PCa cells, but anti-ENO AA sera reacted preferentially with this band in DS cells. Strong immunoreactivity was noted against recENO1 in AA and EA sera (7% vs 28%, p<0.01) and against recENO2 in AA and EA sera (24% vs 35%, p=0.23). EA, but not AA, ENO autoantibodies significantly inhibited DR cell migration, and their pre-absorption with recENO1 diminished this inhibitory effect. CONCLUSIONS: Autoantibodies to ENO1 and ENO2 were identified in EA and AA PCa patient sera. Weaker ENO1 immunoreactivity was seen in sera from AA PCa patients, corresponding with weaker inhibition of DR PCa cell migration compared to EA patient sera. Unlike PSMA and ENO2, ENO1 expression was robust in neuroendocrine-like DR PCa cell lines. Future studies will correlate the presence of ENO autoantibodies with clinicopathologic parameters in a larger patient cohort. Defining mechanisms underlying the race-related differential ENO immunoreactivity may identify novel biological determinants of PCa health disparities and uncover the theranostic potential of tumor surface ENO1. Citation Format: Kai Wen Cheng, Carlos J. Diaz Osterman, Krystal Santiago, Michael Reeves, Diano Lozano, Pedro Ochoa, Alfonso Duran, Saied Mirshahidi, Brian R. Hu, Frankis Almaguel, Carlos A. Casiano. Race-related differential immunoreactivity of enolase autoantibodies in patients with prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2146.

Abstract 7645: Differentially expressed genes as prognostic markers in racial disparities of prostate cancer

Abstract Racial disparities in prostate cancer are prevalent, with African American (AA) men experiencing 60% greater incidence and 2 to 3 times higher mortality than Caucasian American (CA) men. Consequently, there is a pressing need for improved means of interrogating race/ethnicity-based prostate cancer biology in order to identify biomarkers to help stratify men at high-risk for prostate cancer-specific progression and death and offer treatment recommendation that would mostly benefit AA men undergoing early aggressive therapies. Current predictive models rely on clinical variables but do not account for these disparities. The overall goal is to construct a race-specific prostate cancer prognostic prediction model for risk assessment. Here we performed comprehensive bioinformatics analysis using the data from 17 pairs of gene expression array from AA and CA cohorts and identified 63 differentially expressed genes (DEGs) by race. Among them, chemokine receptor 4 (CXCR4), viz. p-Akt (Ser473), fatty acid synthase (FASN), interleukin-6 (IL-6) and matrix metallopeptidase 9 (MMP-9) gene expressions were significantly altered in AA groups. Immunohistochemistry was performed on 163 prostate cancer patient specimens to validate DEG expression and immunoreactive scores (IRS) were calculated. CXCR4 exhibited significantly higher expression in AA tumors, with > 85% of AA prostate tumors showing weak to strong CXCR4 expression, compared to < 5% in CA specimens. While immunostaining for IL-6, FASN, MMP9 and p-Akt did not provide a significant distinction between CA and AA cases. IRS analysis confirmed higher expression of CXCR4 in AA cancers, compared to CA prostate cancer (p < 0.001). MMP9 and IL6 expression were moderately higher in AA cancer compared to CA prostate cancer (p < 0.05). In contrast, FASN expression was significantly higher in CA cancer, compared to AA prostate cancer (p < 0.001). We further investigated the impact of these genes on biochemical recurrence-free survival (BCRFS) using Kaplan-Meier analysis to examine the differences between low-risk versus high-risk groups. BCRFS analysis demonstrated that CXCR4 is a determinant factor of recurrence risk in AA prostate cancer patients. The activation of the PI3K-Akt signaling pathway, particularly in AA patients, suggests its role in prostate cancer aggressiveness. Taken together, this study demonstrates the importance of differential expression of biomarkers which constitute the bulk tumors in driving cancer. The distinct gene expression patterns, especially the upregulation of CXCR4, in AA prostate cancer highlight its potential as a prognostic biomarker and a target for personalized treatment strategies. These findings encourage further study into the role of population-specific difference in adding CXCR4 in risk model construction, especially in machine learning models. Citation Format: Amel A. Ahmed, Shiv Verma, Ibrahim M. Atawia, Daniel L. Shen, Gregory T. MacLennan, Pingfu Fu, Sanjay Gupta. Differentially expressed genes as prognostic markers in racial disparities of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7645.

Abstract 2203: Dietary patterns and prostate cancer risk in the Multiethnic Cohort Study

Abstract Background: A growing body of research has shown the benefits of a healthy diet on a variety of cancer outcomes. Evidence is inconsistent for prostate cancer and research in diverse populations is limited. Methods: In the Multiethnic Cohort Study (MEC), we conducted a prospective cohort analysis to investigate the association of four diet quality indices (DQIs; AHEI-2010, aMED, HEI-2015, DASH; a higher score indicates healthier diet), three plant-based diet indices (PDI, hPDI, uPDI), two inflammatory (DII, EDIP), and two insulinemic dietary indices (EDIH, EDIR) (a higher score indicates more pro-inflammatory or pro-insulinemic diet) with incidence of prostate cancer (PCa) in 79,930 men from five racial/ethnic groups (White, African American, Japanese American, Latino, and Native Hawaiian). All dietary scores were constructed from a baseline quantitative food frequency questionnaire. Outcomes examined included total PCa, high-grade PCa (Gleason score > 7), advanced PCa (regional or distant), aggressive PCa (high-grade or advanced), and lethal PCa (distant or death due to PCa). Hazard ratios (HR) and 95% confidence intervals (CI) per one standard deviation (SD) increase in the dietary score were estimated from Cox proportional hazards models, overall and by race/ethnicity. Associations were considered nominally significant at P < 0.05. Results: During a mean follow-up of 18.9 years, a total of 9,759 incident PCa cases were identified, including 2,503 high-grade, 1,706 advanced, 3,430 aggressive, and 1,426 lethal PCa cases. None of the dietary scores was significantly associated with total PCa. We found a significant association between DII and advanced PCa (HR=1.08, 95% CI=1.01-1.15) overall and the association appeared to be the strongest in African Americans (HR=1.17, 95% CI=1.00-1.36) and Native Hawaiians (HR=1.29, 95% CI=0.98-1.68). We also observed weak associations of the four DQIs with advanced PCa (HR of 0.95-0.96, P of 0.07-0.10) in the overall population, among which a higher DASH score was significantly associated with a 15% (95% CI = 0.75-0.96) lower risk of advanced PCa in African Americans. In addition, we observed that several inflammatory (EDIP) and insulinemic (EDIH, EDIR) dietary scores were associated with lower incidence of advanced, aggressive, or lethal PCa (HR=0.89-0.95, P of 0.03-0.05), which requires further investigation. Conclusions: Our findings suggest that diets with high proinflammatory potential may increase risk of advanced PCa while following a healthy dietary pattern may reduce the risk of advanced PCa. Further studies are needed to better understand the inconsistent results across studies on diet and PCa risk and whether our findings can be replicated in other populations. Citation Format: Wei Xiong, Song-Yi Park, Anqi Wang, Peggy Wan, Lynne R. Wilkens, Loïc Le Marchand, Christopher A. Haiman, Fei Chen. Dietary patterns and prostate cancer risk in the Multiethnic Cohort Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2203.

Abstract 6159: Single cell analysis of circulating peripheral blood mononuclear cells in African American men with prostate cancer and their association with lethal disease

Abstract Prostate cancer is a leading cause of cancer-related deaths among men in the United States and affects African American (AA) men more so than other men. We and others previously described a distinct tumor immunobiology in AA prostate cancer patients. Furthermore, we discovered a serum proteome-defined suppression of tumor immunity signature that is prevalent among these patients and associated with lethal prostate cancer. In the current study, we sought to investigate the composition of circulating peripheral blood mononuclear cells (PBMCs) in AA and European American (EA) prostate cancer patients and their association with patient group and lethal prostate cancer. We obtained high-quality RNA-sequencing data for 277336 single cells representing circulating PBMCs from 59 AA and EA men. In the analysis, being an AA patients associated with an increased abundance of exhausted T cells, higher numbers of plasma B cells and CD16+ monocytes. Gene signatures indicative of T cell exhaustion and Treg activity were generally elevated in AA PBMCs while T cell effector function features were decreased. Within the overall cell population, interferon gene signatures were robustly elevated in AA than EA patients. This gene signature pattern that we observed in AA patients also associated with lethal prostate cancer, namely the T cell exhaustion, Treg activity and elevated interferon signaling gene signatures, may contribute to immune dysfunction and immune injury; pointing to potential clinical implications. Lastly, the interferon-induced transmembrane protein (IFITM3), interferon alpha inducible protein (IFI6), cysteine rich protein-1 (CRIP1), and the RAC family small GTPase2 (RAC2) were notably upregulated in AA patient-derived immune cells. In summary, we show that circulating immune cell populations and the associated gene signatures differ between men of African and European descent. Those elevated in AA patients correlated with lethal prostate cancer. Citation Format: Md Shakir Uddin Ahmed, Tiffany Dorsey, Stefan Ambs. Single cell analysis of circulating peripheral blood mononuclear cells in African American men with prostate cancer and their association with lethal disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6159.

Abstract 2565: Vitamin D deficiency and outcomes in prostate cancer patients: A real-world database

Abstract Introduction: Vitamin D is essential for many bodily functions, including bone health and the prevention of osteoporosis and rickets. In recent years, the importance of vitamin D metabolism in immune system regulation and cancer prevention has been studied with increased focus. With the advent of cancer immunotherapies this has become more important. Multiple recent publications document that vitamin D deficiency is prevalent in cancer patients. This has also been observed specifically in prostate cancer patients, with a high percentage of these deficient patients being of African- American ancestry. It has been theorized that high levels of vitamin D deficiency among African American prostate cancer patients could contribute to worse cancer outcomes and increased health disparities. However, routine vitamin D testing has not been commonly performed in the oncologic community. We hypothesized that deficient levels of vitamin D could lead to inferior prostate cancer outcomes in men with a wide range of ethnic and socio-economic backgrounds. In this project we recorded vitamin D levels in prostate cancer patients at a large community oncology group and evaluated them by stage, pathologic data, survival, race/ethnicity, and other clinical features. Methods: This study is a retrospective, observational study of the data from the electronic medical records of patients with prostate cancer who received vitamin D level testing at Florida Cancer Specialists & Research Institute from 2008- 2023, throughout the state of Florida. All data used in this study will constitute secondary data, it will have been collected originally for clinical use in the general oncology practice setting. No date parameters or patient limits will be applied to this study, and all eligible patients are included. Results: 451 patients with prostate cancer had determination of vitamin D levels, out of a total of 27,772 prostate cancer patients in the database. 38% of the prostate cancer patients analyzed had low 25-OH vitamin D levels (<32 ng/ml). Patients with low vitamin D levels had an average Gleason score of 7.46. Patients with low vitamin D levels who died had an average survival of 144 months. Patients with low vitamin D levels who presented with localized disease had a 35% chance of eventually developing castrate-resistant disease. 45% of the low vitamin D group developed metastatic disease during their course of treatment. Further comparisons of vitamin D levels with pathologic data, survival/longevity, race/ethnicity, and clinical course will be evaluated and presented. Citation Format: Lowell L. Hart, James Reeves, Stacey Garofalo, William Amick. Vitamin D deficiency and outcomes in prostate cancer patients: A real-world database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2565.

Abstract 773: Overexpression of phosphoserine phosphatase (PSPH) in prostate cancer and in tumor microenvironment promotes tumor cell proliferation

Abstract Reprogrammed cellular metabolism is one of the key features of cancer and tumor microenvironment. L-3-phosphoserine phosphatase (PSPH) is one of the five rate-limiting enzymes in the biosynthesis of serine from glucose that supports cell proliferation. Here, we aim to study the role of PSPH in prostate cancer (PCa) and its tumor microenvironment. We find that PSPH not only is overexpressed in prostate cancer cell lines compared to normal prostate epithelial cells (PrEC) and benign prostate epithelial cells (BPH-1), but also exhibits a higher level in patient-derived carcinoma-associated fibroblasts (CAFs) compared to the matched benign associated fibroblasts (BAFs), which are derived from fresh radical prostatectomy specimens of African American (AA) and European American (EA) men. Notably, MDAPCa2b cells derived from an AA prostate cancer patient and AA CAFs have even higher expression of PSPH protein. The mRNA levels of PSPH are also significantly elevated in prostate cancer tissues in AA men compared to EA men and predict poor survival in PCa patients. Knock-down of PSPH expression significantly inhibits the proliferation and colony formation of prostate cancer cells. Growth of xenograft tumors derived from PSPH knockdown MDAPCa2b cells has also been suppressed markedly. Gene expression profiling revealed that suppression of PSPH expression by shRNAs in LNCaP and MDAPCa2b cells is associated with the regulation of gene expression related to metabolism, immunity, extracellular matrix remodeling, and Ion channels. Similarly, analysis of publicly available PCa RNA seq databases also demonstrates that PSPH amplification or over-expression is associated with alterations of gene expression related to metabolism and immunity. Our results suggest that PSPH is upregulated in prostate cancer cells and their surrounding fibroblasts to support tumor growth via reprogramming metabolic pathways and transcriptomes. Citation Format: Liankun Song, Noriko Yokoyama, Jun Xie, Yunjie Hu, Zhenyu (Arthur) Jia, Beverly Wang, Dan Mercola, Edward Uchio, Thomas Ahlering, Michael Lilly, Xiaolin Zi. Overexpression of phosphoserine phosphatase (PSPH) in prostate cancer and in tumor microenvironment promotes tumor cell proliferation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 773.

Abstract 2148: Tumor-microenvironment from African-American prostate cancer exhibit methylation of multiple immune modulators

Abstract Background: Non-Hispanic Black American patients (BA) with prostate cancer (PCa) tend to fare worse than their Non-Hispanic White American counterparts (WA), even with consideration of socioeconomic disparities. Clinically, BA face diagnosis at younger age with worse clinical outcomes. Stromal cells adjacent to the tumor, including carcinoma-associated fibroblasts (CAFs), play a critical role in tumorigenesis of PCa. Dysfunction in the tumor microenvironment play a crucial role in mediating prostate cancer tumorigenesis and is emerging as a key target for cancer therapy in solid tumors. Methods: To investigate whether DNA methylation varies in tumor adjacent stroma (TAS) among PCa patients with different geographical ancestries, areas immediate adjacent to tumor (i.e., less than 1mm) removed for methylation analysis. A complete genome-wide DNA methylation of PCa stroma using 17 BA and 15 WA patients who had radical prostatectomy was carried out. Methyl-Captured (mCap) sequencing data was generated for TAS of prostate cancer FFPE tissues. Methylated sites were identified with the MACS2 callpeak function using a band width of 300 bp and a false discovery rate of q < 0.05. A consensus peak set was derived from the aligned reads of BA and WA prostate cancer stroma samples that were sequenced. Pathway analysis was performed using Ingenuity Pathway Analysis (IPA) tools. CAFs from primary tumors of BA and WA was prepared by tissue culture and treated with demethylating agent (i.e., 5-Azacytidine) for 24 hours followed by maintenance of the cells in drug-free medium for 7-10 days and subjected to mCap sequencing. Results: We found racial disparities in genome-wide DNA methylation in TAS between the two populations in which BA PCa patients had significantly increased in global DNA methylation as compared to their WA counterpart (p value < 0.001). Hypomethylation occurred in CAFs from BA patients treated with 5-Azacytidine. We identified 1041 methylated sites corresponding to 409 unique genes that were differentially methylated in BA vs WA (p value < 0.05). Pathway analysis identified significant association between methylated genes in BA TAS and immune response pathways including IL-13, JACK/STAT, T cell receptors, NF-KB, and PD-1, PDL1 cancer immunotherapy. Evaluation of the methylome profile between patients based on the post-prostatectomy resection margins, negative (R0) vs positive (R1), showed that R0 resections had significantly greater (p value < 0.001) methylation than R1 resections. Further analysis identified 984 sites corresponding to 373 differentially methylated, unique genes (p value < 0.05). Conclusion: Tumor-adjacent stroma of BA prostate cancer patients has a distinct methylome as compared to WA patients. Differences in immune response pathways suggests a distinct immune response in TAS in men of different races. Citation Format: Santosh Sankaran, James Nguyen, Tara Jennings, Vinay Kumar, Michael B. Lilly, Michael M. Ittmann, Patricia Castro, Liankun Song, Thomas Keane, Weiping Chu, Xiaolin Zi, Omid Yazdanpanah, Arash Rezazadeh Kalebasty, Farah Rahmatpanah. Tumor-microenvironment from African-American prostate cancer exhibit methylation of multiple immune modulators [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2148.

A west African ancestry-associated SNP on 8q24 predicts a positive biopsy in African American men with suspected prostate cancer following PSA screening.

African American (AA) men have the highest incidence and mortality rates of prostate cancer (PCa) among all racial groups in the United States. While race is a social construct, for AA men, this overlaps with west African ancestry. Many of the PCa susceptibility variants exhibit distinct allele frequencies and risk estimates across different races and contribute substantially to the large disparities of PCa incidence among races. We previously reported that a single-nucleotide polymorphism (SNP) in 8q24, rs7824364, was strongly associated with west African ancestry and increased risks of PCa in both AA and Puerto Rican men. In this study, we determined whether this SNP can predict biopsy positivity and detection of clinically significant disease (Gleason score [GS] ≥ 7) in a cohort of AA men with suspected PCa. SNP rs7824364 was genotyped in 199 AA men with elevated total prostate-specific antigen (PSA) (>2.5 ng/mL) or abnormal digital rectal exam (DRE) and the associations of different genotypes with biopsy positivity and clinically significant disease were analyzed. The variant allele carriers were significantly over-represented in the biopsy-positive group compared to the biopsy-negative group (44% vs. 25.7%, p = 0.011). In the multivariate logistic regression analyses, variant allele carriers were at a more than a twofold increased risk of a positive biopsy (odds ratio [OR] = 2.14, 95% confidence interval [CI] = 1.06-4.32). Moreover, the variant allele was a predictor (OR = 2.26, 95% CI = 1.06-4.84) of a positive biopsy in the subgroup of patients with PSA < 10 ng/mL and normal DRE. The variant allele carriers were also more prevalent in cases with GS ≥ 7 compared to cases with GS < 7 and benign biopsy. This study demonstrated that the west African ancestry-specific SNP rs7824364 on 8q24 independently predicted a positive prostate biopsy in AA men who were candidates for prostate biopsy subsequent to PCa screening.

Examining the role of social relationships on health and health behaviors in African American men with prostate cancer: a qualitative analysis.

Cancer survivor cohort studies document the positive impact of health behaviors on cancer survivorship by influencing quality of life, comorbidity burden, and cancer recurrence. Social networks can be instrumental in supporting health behavior changes. This study used qualitative interviews to explore how social networks may impact health and health behaviors of African American Prostate Cancer Survivors (AAPCS) enrolled in Men Moving Forward (MMF), a lifestyle intervention designed with and for AAPCS. Specifically, we sought to understand how different relationships within social networks influence health and health behaviors, and to identify potential mechanisms for this influence. Eighteen men who completed the MMF intervention participated in a semi-structured interview which explored social connections, health and health behaviors, stress, and the cancer experience. Interviews were recorded and transcribed, and thematic analysis was performed by two coders. Participants described robust social networks of friends and family. Four distinct yet overlapping themes were identified that described how relationships influence health and health behaviors among AAPCS: (1) provision of knowledge, (2) health and behavior history, (3) encouragement and support, and (4) shared behavior. These results provide initial insight into the types of relationships that influence health, and the intersecting and multifaceted mechanisms through which this influence occurs.

Association of neighborhood gentrification with prostate cancer and immune markers in African American and European American men.

Prior studies showed that neighborhood deprivation increases the risk of lethal prostate cancer. However, the role of neighborhood gentrification in prostate cancer development and outcome remains poorly understood. We examined the relationships of gentrification with prostate cancer and serum proteome-defined inflammation and immune function in a diverse cohort. The case-control study included 769 cases [405 African American (AA), 364 European American (EA) men] and 1023 controls (479 AA and 544 EA), with 219 all-cause and 59 prostate cancer-specific deaths among cases. Geocodes were linked to a neighborhood gentrification index (NGI) derived from US Census data. Cox and logistic regression, and MANOVA, were used to determine associations between NGI, as continuous or quintiles (Q), and outcomes. Adjusting for individual socioeconomic status (SES), continuous NGI was positively associated with prostate cancer among all men (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.01-1.14). AA and low-income men experienced the highest odds of prostate cancer when residing in tracts with moderate gentrification, whereas EA men experienced reduced odds of regional/metastatic cancer with increased gentrification in SES-adjusted analyses. Continuous NGI also associated with mortality among men presenting with localized disease and low-income men in SES-adjusted Cox regression analyses. NGI was not associated with serum proteome-defined chemotaxis, inflammation, and tumor immunity suppression. Findings show that neighborhood gentrification associates with prostate cancer and mortality in this diverse population albeit associations were heterogenous within subgroups. The observations suggest that changing neighborhood socioeconomic environments may affect prostate cancer risk and outcome, likely through multifactorial mechanisms.

Abstract C061: The impact of the BRG1/BRM-associated factor (BAF) complex on the androgen receptor cistrome in African American prostate cancer

Abstract We aimed to establish in prostate cancer (PCa) how and why the androgen receptor displays differential functions in a manner driven by genomic ancestry, namely between African American (AA) and European American (EA) PCa, with the goal to assess how this may contribute to PCa health disparities. We utilized EA and AA non-malignant prostate and PCa cell models with confirmed genomic ancestry and defined the basal and dihydrotestosterone (DHT)-regulated AR and H3K27ac cistromes using CUT&amp;RUN, and integrated these data with publicly available genomic counterparts. The DHT-dependent AR and H3K27ac cistromes significantly overlapped within AA cells and EA cells but there was significantly less overlap between AA and EA cells. For example, H3K27ac distributions were frequent (~15-20k sites) in each of non-malignant AA RC43N and EA HPr1AR, and malignant RC43T and LNCaP, and the significance of the overlaps were comparable for basal and DHT treated cells, but this was not significantly impacted by ancestry. By contrast the AR cistrome was highly DHT-dependent, with ~2k sites notably in LNCaP and RC43T, which very significantly overlapped with H3K27ac in the same cells but significantly less so across cells. Thus, although the H3K27ac cistrome was comparable across cells, the overlap with AR was driven by genomic ancestry. To investigate this, we focused on the BAF complexes as previously we identified reduced expression of a key component, SMARCA5, in AA PCa. These large multimeric complexes regulate nucleosome positioning during gene transcription and DNA repair. In PCa, the cBAF complex impacts different transcription factors, including ERG, and it is tempting to speculate that the corruption of cBAF identified in AA PCa phenocopies the impact of TMPRSS2-ETS impact observed in EA PCa. To test the possibility that the cBAF complex corrupts AR genomic functions in AA PCa we exploited scRNA-Seq data from PCa organoids from the Rb and Pten double knockout (PBCre4:Rb1f/f:Pten f/f ) to establish that expression of genes in the cBAF genes complex were collectively significantly altered in neuroendocrine PCa (NEPC) and Pouf23 androgen indifferent lineages. Secondly, knockdown of another cBAF component, SMARCC1, enhanced Enzalutamide sensitivity in same organoids. Finally, to test the impact of cBAF complex on AR signaling we have generated AA and EA PCa cell lines that stably express dCRISPR-activator (VP64) or repressor (KRAB) proteins and designed gRNAs to regulate expression of, for example, SMARCA5 and measure the impact on the AR cistrome and function. In summary, these findings identified that the shared AR and H3K27ac cistromes are driven by genomic ancestry, and that reduced expression of SMARCA5 and other components of the cBAF complex are significant in AA and advanced PCa, and impact AR signaling. Our future directions are focused on how SMARCA5 expression disrupts the balance between transcription factor functions, such as for the AR and other transcription factors, and effective DNA repair. Citation Format: Shahid S. Hussain, Debasis Nayak, David W. Goodrich, Clayton Yates, Moray Campbell. The impact of the BRG1/BRM-associated factor (BAF) complex on the androgen receptor cistrome in African American prostate cancer [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C061.

Abstract B088: Association of neighborhood gentrification with prostate cancer in African American and European American men

Abstract Abstract Background: Prior studies showed that neighborhood deprivation increases the risk of lethal prostate cancer. However, the role of neighborhood gentrification in prostate cancer development and outcome remains poorly understood. We examined the relationships of gentrification with prostate cancer in a diverse cohort. Methods: This case-control study included 769 cases [405 African American (AA), 364 European American (EA) men] and 1023 controls (479 AA, 544 EA), with 219 all-cause and 59 prostate cancer-specific deaths among cases. Geocodes were linked to a neighborhood gentrification index (NGI) derived from US Census data. Cox and logistic regression were used to determine associations between NGI, as continuous or quintiles (Q), and outcomes. Results: Adjusting for individual socioeconomic status (SES), continuous NGI was associated with prostate cancer among all men (odds ratio (OR) 1.07, 95%CI 1.01-1.14). AA experienced the highest odds of prostate cancer when residing in tracts with moderate gentrification (Q3 OR 1.79, 95%CI 1.11-2.88). However, EA men experienced a reduced risk of regional/metastatic cancer (risk ratio 0.62, 95%CI 0.40-0.97) with increased gentrification, adjusting for SES. Continuous NGI was associated with mortality among men presenting with localized disease (all-cause HR 1.10, 95%CI 1.01-1.20; disease-specific SHR 1.16, 95%CI: 1.01-1.33). Conclusions: Findings show that neighborhood gentrification modestly associates with prostate cancer and mortality in this diverse population. They suggest that changing neighborhood socioeconomic environments may affect prostate cancer risk and outcome, likely through multifactorial mechanisms. Citation Format: Catherine M. Pichardo, Adaora Ezeani, Margaret Pichardo, Tanya Agurs-Collins, Tiffany M. Powell-Wiley, Brid Ryan, Tsion Minas, Maeve Bailey-Whyte, Wei Tang, Tiffany H. Dorsey, William Wooten, Christopher A. Loffredo. Association of neighborhood gentrification with prostate cancer in African American and European American men [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B088.