Survival In Epithelial Ovarian Cancer Research Articles

Amphiregulin Downregulates E-cadherin Expression by Activating YAP/Egr-1/Slug Signaling in SKOV3 Human Ovarian Cancer Cells

Amphiregulin Downregulates E-cadherin Expression by Activating YAP/Egr-1/Slug Signaling in SKOV3 Human Ovarian Cancer Cells

High histone H3K18 lactylation level is correlated with poor prognosis in epithelial ovarian cancer.

Protein lactylation has a poor prognosis in malignant tumors, but its impact on the prognosis of epithelial ovarian cancer (EOC) remains unknown. We analyzed 112 patients with EOC. Immunohistochemical staining was used to detect the level of pan lactylation (Pan Kla) and histone H3K18 lactylation (H3K18la) in the EOC tissues and normal ovarian tissues. The result showed that the protein lactylation level in EOC was higher than in normal tissues. Then, we analyzed the relationship between overall survival (OS), progression-free survival (PFS) of EOC, and lactylation. The result showed that patients with high histone H3K18la levels had poorer OS (p=0.028) and PFS (p<0.001). Multivariate Cox regression analysis of PFS showed histone H3K18la was an independent risk factor (p=0.001). In addition, we found that both histone H3K18la and Pan Kla in the cytoplasm were associated with platinum recurrence time (p=0.002/p=0.003). The results also indicated that the H3K18la level was related to a tumor stage (p=0.037). Furthermore, we explored the effects of lactylation on the metastasis of ovarian cancer. The results indicated a significant increase in migration in the promoter group compared to the negative control group and inhibitor group. In conclusion, high histone H3K18la level is associated with poor prognosis in EOC. Protein lactylation may have a significant impact on EOC and could potentially be used as a target for EOC therapy in the future.

The effect of tinzaparin on biomarkers in FIGO stages III-IV ovarian cancer patients undergoing neoadjuvant chemotherapy - the TABANETOC trial: study protocol for a randomized clinical multicenter trial.

Tinzaparin, a low-molecular weight heparin (LMWH), has shown anti-neoplastic properties in animal models and in in vitro studies of human cancer cell lines. The reduction of CA-125 levels during neoadjuvant chemotherapy (NACT) in patients with epithelial ovarian cancer (EOC) co-varies with the prognosis; the larger the decrease in CA-125, the better the prognosis. This study aims to evaluate the potential anti-neoplastic effects of tinzaparin by investigating changes in serum CA-125 levels in advanced EOC patients who receive NACT. This is an open randomized multicenter pilot trial. Forty patients with EOC selected to receive NACT will be randomized 1:1 to receive daily addition of tinzaparin or no tinzaparin. The processing and treatment of the patients will otherwise follow the recommendations in the Swedish National Guidelines for Ovarian Cancer. Before every cycle of chemotherapy, preoperatively, and 3 weeks after the last cycle of chemotherapy, a panel of biomarkers, including CA-125, will be measured. Inclusion criteria are women aged 18 years or older, World Health Organization performance status 0-1, histologically confirmed high-grade serous, endometrioid or clear cell EOC, International Federation of Gynecology and Obstetrics (FIGO) stages III-IV. In addition, a CA-125 level of ≥ 250 kIE/L at diagnosis. Exclusion criteria are contraindications to LMWH, ongoing or recent treatment with unfractionated heparin, LMWH, warfarin or non-vitamin K antagonist oral anticoagulants. This study will make an important contribution to the knowledge of the anti-neoplastic effects of tinzaparin in EOC patients and may thus guide the planning of a future study on the impact of tinzaparin on survival in EOC.

Asian American sub-ethnic disparities and trends in epithelial ovarian cancer diagnosis, treatment and survival

ABSTRACT Objectives Studies on ovarian cancer (OC) diagnosis, treatment and survival across disaggregated Asian sub-ethnic groups are sparse. Few studies have also conducted trend analyses of these outcomes within and across Asian groups. Methods Using logistic, Cox, and Joinpoint regression analyses of the 2000–2018 Surveillance, Epidemiology, and End Results (SEER) data, we examined disparities and trends in OC advanced stage diagnosis, receipt of treatments and the 5-year cause-specific survival across seven Asian sub-ethnic groups. Results There were 6491 OC patients across seven Asian sub-ethnic groups (mean [SD] age, 57.29 [13.90] years). There were 1583(24.39%) Filipino, 1183(18.23%) Chinese, and 761(11.72%) Asian Indian or Pakistani (AIP) patients. The majority (52.49%) were diagnosed with OC with at an advanced stage. AIP were more likely to have advanced stage diagnosis than other subgroups (ORs, 95%CIs: 0.77, 0.62−0.96 [Filipino]; 0.76, 0.60−0.95 [Chinese]; 0.71, 0.54−0.94 [Japanese]; 0.74, 0.56−0.98 [Vietnamese] and 0.66, 0.53−0.83 [Other Asians]). The Filipinos were least likely to receive surgery but most likely to undergo chemotherapy. Japanese patients had the worst 5-year OC cause-specific survival (50.29%, 95%CI: 46.20%−54.74%). Based on the aggregated analyses, there was a significantly decreased trend in advanced-stage diagnosis and an increased trend in receipt of chemotherapy. Trends in OC outcomes for several subethnicities differed from those observed in aggregated analyses. Conclusion In this cohort study of 6491 patients, OC diagnosis, treatment, survival, and trends differed across Asian American ethnic subgroups. Such differences must be considered in future research and interventions to ensure all Asian American subethnicities equally benefit from the advancements in OC care and control.

Prediction of ovarian cancer prognosis using statistical radiomic features of ultrasound images

Objective. Ovarian cancer is the deadliest gynecologic malignancy worldwide. Ultrasound is the most useful non-invasive test for preoperative diagnosis of ovarian cancer. In this study, by leveraging multiple ultrasound images from the same patient to generate personalized, informative statistical radiomic features, we aimed to develop improved ultrasound image-based prognostic models for ovarian cancer. Approach. A total of 2057 ultrasound images from 514 ovarian cancer patients, including 355 patients with epithelial ovarian cancer, from two hospitals in China were collected for this study. The models were constructed using our recently developed Frequency Appearance in Multiple Univariate pre-Screening feature selection algorithm and Cox proportional hazards model. Main results. The models showed high predictive performance for overall survival (OS) and recurrence-free survival (RFS) in both epithelial and nonepithelial ovarian cancer, with concordance indices ranging from 0.773 to 0.794. Radiomic scores predicted 2 year OS and RFS risk groups with significant survival differences (log-rank test, P < 1.0 × 10−4 for both validation cohorts). OS and RFS hazard ratios between low- and high-risk groups were 15.994 and 30.692 (internal cohort) and 19.339 and 19.760 (external cohort), respectively. The improved performance of these newly developed prognostic models was mainly attributed to the use of multiple preoperative ultrasound images from the same patient to generate statistical radiomic features, rather than simply using the largest tumor region of interest among them. The models also revealed that the roundness of tumor lesion shape was positively correlated with prognosis for ovarian cancer. Significance. The newly developed prognostic models based on statistical radiomic features from ultrasound images were highly predictive of the risk of cancer-related death and possible recurrence not only for patients with epithelial ovarian cancer but also for those with nonepithelial ovarian cancer. They thereby provide reliable, non-invasive markers for individualized prognosis evaluation and clinical decision-making for patients with ovarian cancer.

Impact of insomnia on ovarian cancer risk and survival: a Mendelian randomization study

Insomnia is the most common sleep disorder in patients with epithelial ovarian cancer (EOC). We investigated the causal association between genetically predicted insomnia and EOC risk and survival through a two-sample Mendelian randomization (MR) study. Insomnia was proxied using genetic variants identified in a genome-wide association study (GWAS) meta-analysis of UK Biobank and 23andMe. Using genetic associations with EOC risk and overall survival from the Ovarian Cancer Association Consortium (OCAC) GWAS in 66,450 women (over 11,000 cases with clinical follow-up), we performed Iterative Mendelian Randomization and Pleiotropy (IMRP) analysis followed by a set of sensitivity analyses. Genetic associations with survival and response to treatment in ovarian cancer study of The Cancer Genome Atlas (TCGA) were estimated controlling for chemotherapy and clinical factors. Insomnia was associated with higher risk of endometrioid EOC (OR=1.60, 95% CI 1.05-2.45) and lower risk of high-grade serous EOC (HGSOC) and clear cell EOC (OR=0.79 and 0.48, 95% CI 0.63-1.00 and 0.27-0.86, respectively). In survival analysis, insomnia was associated with shorter survival of invasive EOC (OR=1.45, 95% CI 1.13-1.87) and HGSOC (OR=1.4, 95% CI 1.04-1.89), which was attenuated after adjustment for body mass index and reproductive age. Insomnia was associated with reduced survival in TCGA HGSOC cases who received standard chemotherapy (OR=2.48, 95% CI 1.13-5.42), but was attenuated after adjustment for clinical factors. This study supports the impact of insomnia on EOC risk and survival, suggesting treatments targeting insomnia could be pivotal for prevention and improving patient survival. National Institutes of Health, National Cancer Institute. Full funding details are provided in acknowledgments.

The association of body composition phenotypes before chemotherapy with epithelial ovarian cancer mortality.

The association of body composition with epithelial ovarian carcinoma (EOC) mortality is poorly understood. To date, evidence suggests high adiposity associates with decreased mortality (an obesity paradox), but the impact of muscle on this association has not been investigated. Herein, we define associations of muscle and adiposity joint-exposure body composition phenotypes with EOC mortality. Body composition from 500 women in The Body Composition and Epithelial Ovarian Cancer Survival Study was dichotomized as normal/low skeletal muscle index (SMI), a proxy for sarcopenia and high/low adiposity. Four phenotypes were classified as fit/reference (normal SMI/low adiposity; 16.2%), overweight/obese (normal SMI/high adiposity; 51.2%), sarcopenia/overweight-obese (low SMI/high adiposity; 15.6%), and sarcopenia/cachexia (low SMI/low adiposity; 17%). We used multivariable Cox models to estimate associations of each phenotype with mortality for EOC overall and high-grade serous ovarian carcinoma (HGSOC). Overweight/obesity was associated with up to 51% and 104% increased mortality in EOC and HGSOC (HR = 1.51, 95% CI: 1.05-2.19 and HR = 2.04, 95% CI: 1.29-3.21). Sarcopenia/overweight-obesity was associated with up to 66% and 67% increased mortality in EOC and HGSOC (HR = 1.66, 95% CI: 1.13-2.45 and HR = 1.67, 95% CI: 1.05-2.68). Sarcopenia/cachexia was associated with up to 73% and 109% increased mortality in EOC and HGSOC (HR = 1.73, 95% CI: 1.14-2.63 and HR = 2.09, 95% CI: 1.25-3.50). Overweight/obesity, sarcopenia/overweight-obesity and sarcopenia/cachexia phenotypes were each associated with increased mortality in EOC and HGSOC. Exercise and dietary interventions could be leveraged as ancillary treatment strategies for improving outcomes in the most fatal gynecological malignancy with no previously established modifiable prognostic factors.

Selective targeting of IRAK1 attenuates low molecular weight hyaluronic acid-induced stemness and non-canonical STAT3 activation in epithelial ovarian cancer

Advanced epithelial ovarian cancer (EOC) survival rates are dishearteningly low, with ~25% surviving beyond 5 years. Evidence suggests that cancer stem cells contribute to acquired chemoresistance and tumor recurrence. Here, we show that IRAK1 is upregulated in EOC tissues, and enhanced expression correlates with poorer overall survival. Moreover, low molecular weight hyaluronic acid, which is abundant in malignant ascites from patients with advanced EOC, induced IRAK1 phosphorylation leading to STAT3 activation and enhanced spheroid formation. Knockdown of IRAK1 impaired tumor growth in peritoneal disease models, and impaired HA-induced spheroid growth and STAT3 phosphorylation. Finally, we determined that TCS2210, a known inducer of neuronal differentiation in mesenchymal stem cells, is a selective inhibitor of IRAK1. TCS2210 significantly inhibited EOC growth in vitro and in vivo both as monotherapy, and in combination with cisplatin. Collectively, these data demonstrate IRAK1 as a druggable target for EOC.

Correlation between peritoneal cancer index and survival in advanced epithelial ovarian cancer with complete resection

ObjectiveThe aim of this study was to investigate the relation between the peritoneal cancer index, overall survival, and recurrence free survival, in patients with epithelial ovarian cancer.MethodsPatients treated at the...

Prediagnostic use of menopausal hormone therapy and long-term survival of localized epithelial ovarian cancer: The Extreme study.

Use of menopausal hormone therapy (MHT) prior to an epithelial ovarian cancer (EOC) diagnosis has been suggested to be associated with improved survival. In a recent nationwide cohort study, we found that prediagnostic long-term MHT use, especially estrogen therapy (ET), was associated with improved long-term survival in women with nonlocalized EOC. Our aim was to investigate the influence of prediagnostic MHT use on long-term survival among women with localized EOC in the same nationwide study. Our study cohort comprised all women aged 50 years or older with an EOC diagnosis in Denmark 2000-2014 (n = 2097) identified from the Extreme study. We collected information on usage of systemic ET and estrogen plus progestin therapy (EPT) from the Danish National Prescription Registry. By using pseudo-values, 5- and 10-year absolute and relative survival probabilities were estimated with 95% confidence intervals (CIs) while adjusting for histology, comorbidity, and income. Relative survival probabilities >1 indicate better survival. The 5-year absolute survival probabilities were 61% and 56%, respectively, among women who were nonusers and users of prediagnostic MHT, whereas these numbers were 46% and 41%, respectively, regarding 10-year survival. Use of MHT was not significantly associated with an improved 5- or 10-year survival in women with localized EOC (5-year relative survival probability = 0.95, 95% CI: 0.89-1.02; 10-year relative survival probability = 0.92, 95% CI: 0.84-1.02). Similar findings were seen for systemic ET or EPT use. Our findings do not suggest a positive benefit from prediagnostic MHT use on long-term survival of localized EOC.

Correlation between plasma PSGL-1 and FIGO stage, tumor metastasis, and survival in epithelial ovarian cancer.

Plasma circulating P-selectin glycoprotein ligand-1 (PSGL-1) levels and its clinical correlation in patients with epithelial ovarian cancer (EOC) are unknown. The study determined plasma PSGL-1 levels in EOC patients and investigated its relationship with clinicopathological factors and prognosis. Plasma PSGL-1 levels were measured using ELISA in 69 patients with EOC, 34 patients with benign ovarian cystadenoma, and 36 healthy controls. Subsequently, the relationship between PSGL-1 levels and clinicopathological characteristics of patients, as well as the prognosis of EOC patients, was examined. Additionally, the specificity and sensitivity of plasma PSGL-1 were assessed through ROC curve analysis. Plasma PSGL-1 was upregulated in EOC patients compared with healthy subjects and/or patients with benign ovarian cystadenoma (p < 0.01). Elevated levels of PSGL-1 in the plasma were positively associated with advanced FIGO stage (p < 0.001), tumor size (p = 0.001), tumor metastasis (p = 0.036), and tumor recurrence (p = 0.013), while was negatively correlated with residual tumor size (p < 0.001). Kaplan-Meier survival analysis showed that high plasma PSGL-1 levels were associated with progression-free survival (p = 0.0345). In univariate and multivariate Cox regression analyses, PSGL-1 (HR = 1.456, p = 0.009) was an independent prognostic marker. Plasma PSGL-1 levels distinguished EOC patients and healthy individuals (AUC = 0.905), patients at late and early FIGO stages (AUC = 0.886), and metastatic and non-metastatic EOC (AUC = 0.722). The expression of plasma PSGL-1 is significantly increased in patients with EOC, serving as a reliable biomarker to differentiate between healthy individuals and those with EOC. Furthermore, PSGL-1 in patients is correlated with prognostic indicators, such as advanced FIGO stage, tumor lymph node metastasis, and progression-free survival.

Abstract A089: Influence of pre-diagnosis aspirin use on epithelial ovarian cancer tumor immune microenvironment markers: results from the Nurses’ Health Study (NHS) and NHSII

Abstract Background: Daily aspirin use versus never use is associated with a 10-20% lower risk of developing epithelial ovarian cancer (EOC). Among women with EOC, aspirin use after diagnosis compared with never use is associated with a 30% improvement in ovarian cancer-specific survival. Inhibition of enzymes in prostaglandin synthesis is a key mechanism responsible for the anti-inflammatory and anti-neoplastic effects of aspirin. Prostaglandins influence immune inflammatory cells in the tumor microenvironment therefore our objective was to evaluate how aspirin use may influence the EOC tumor immune microenvironment. Methods: Tissue microarrays (TMAs) representing EOC tumor tissues from participants in the Nurses’ Health Study (NHS) and NHSII were assessed for total T cells, T cell activation and T cell exhaustion markers within the tumor (epithelium) area using multiplex immunofluorescence. Data on aspirin use and information on EOC risk factors and lifestyle variables were collected by questionnaire every two years. Beta-binomial models were used to estimate odds ratios (ORs) and 95% CIs; these models estimate the odds that a cell was positive for the marker(s) of interest comparing recent regular aspirin use (2+ times per week in the questionnaire cycle prior to diagnosis) versus never use, accounting for the total tumor cells in each core. Former users of aspirin were excluded. Multivariable models were adjusted for cohort, histotype (type 1 versus type 2), age and year of cancer diagnosis, number of CD3+ T cells (in tertiles), hysterectomy, tubal ligation, duration of oral contraceptive use, family history of breast or ovarian cancer, parity and body mass index (as fixed effects) and the participant (random effect) to account for multiple tissue cores per case. Results: We compared tumor tissues from 209 participants with recent pre-diagnosis use of aspirin with 88 participants who never used aspirin. Compared with cases who never used aspirin, recent aspirin users had higher odds of having tumors with recently activated cytotoxic T cells (CD3+CD8+CD69+, OR=1.69, 95% CI: 1.10, 2.59) and T cells expressing exhaustion markers (CD3+Lag-3+, OR=1.63, 95% CI: 1.09, 2.43; CD3+Tim-3+, OR= 1.62, 95% CI: 0.96, 2.72). In contrast, there was no association between recent aspirin use versus never use and odds of a tumor being positive for total T cells (CD3+, OR=1.20, 95% CI: 0.80, 1.79). Conclusions: Our data suggest that recent aspirin use before diagnosis was associated with higher odds of having EOC tumors expressing both recently activated cytotoxic T cells and T cell exhaustion markers. By improving our biological understanding of how aspirin use influences the ovarian tumor immune microenvironment, these results will assist to inform the optimal use of aspirin to improve EOC patient outcomes. Future work will focus on additional immune markers, assess non-aspirin nonsteroidal anti-inflammatory drug (NSAID) use and evaluate associations between aspirin/NSAID use with EOC survival considering the context of tumor immune microenvironment biomarkers. Citation Format: Nicola S. Meagher, Cassandra Hathaway, Mary K. Townsend, Mollie E. Barnard, Jose R. Conejo-Garcia, Brooke L. Fridley, Daryoush Saeed-Vafa, Britton Trabert, Shelley S. Tworoger, Melissa A. Merritt. Influence of pre-diagnosis aspirin use on epithelial ovarian cancer tumor immune microenvironment markers: results from the Nurses’ Health Study (NHS) and NHSII [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A089.

Abstract B113: Associations between risk factors and epithelial ovarian cancer survival by racial and ethnic group: an analysis from the ovarian cancer association consortium

Abstract B113: Associations between risk factors and epithelial ovarian cancer survival by racial and ethnic group: an analysis from the ovarian cancer association consortium

Collaborative expertise of gynecological and surgical oncologists in managing advanced epithelial ovarian cancer

BackgroundMost patients with epithelial ovarian cancer (EOC) present with significant peritoneal spread. We assessed collaborative efforts of surgical and gynecological oncologists with expertise in cytoreductive surgery (CRS) in the management of advanced EOC. MethodsUsing a prospective single-center database (2014–2022), we described the operative and oncologic outcomes of stage IIIC-IVA primary and recurrent EOC perioperatively managed jointly by gynecological and surgical oncologists both specializing in CRS and presented components of this collaboration. ResultsOf 199 identified patients, 132 (66 %) had primary and 53 (27 %) had recurrent EOC. Due to inoperable disease, 14 (7 %) cases were aborted and excluded from analysis. Median peritoneal cancer index (PCI) in primary and recurrent patients was 21 (IQR: 11–28) and 21 (IQR: 6–31). Upper abdominal surgery was required in 95 % (n = 125) of primary and 89 % (n = 47) of recurrent patients. Bowel resections were performed in 83 % (n = 110) and 72 % (n = 38), respectively. Complete cytoreduction (CC-0/1) with no disease or residual lesions <2.5 mm was achieved in 95 % (n = 125) of primary and 91 % (n = 48) of recurrent patients. Ninety-day Clavien-Dindo grade III-IV morbidity was 12 % (n = 16) and 21 % (n = 11), respectively. Median follow-up was 44 (95%CI: 33–55) months. Median overall survival in primary and recurrent EOC was 68 (95%CI: 45–91) and 50 (95%CI: 16–84) months. Median progression-free survival was 26 (95%CI: 22–30) and 14 (95%CI: 7–21) months, respectively. ConclusionsPerioperative collaboration between surgical and gynecological oncologists specializing in CRS allows safe performance of complete cytoreduction in the majority of patients with primary and recurrent EOC, despite high tumor burden.

Epithelial ovarian cancer survival by race and ethnicity in an equal-access healthcare population

BackgroundPrevious studies in the general population observed that compared with non-Hispanic White women, Pacific Islander and Black women have higher age-adjusted mortality rates from epithelial ovarian cancer (EOC), while Asian American patients have lower mortality. We investigated whether race and ethnicity is associated with differences in EOC survival in a United States Military population where patients have equal access to healthcare.MethodsThis retrospective study included women diagnosed with EOC between 2001 and 2018 among Department of Defense beneficiaries. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models adjusting for age and year of diagnosis, histology and stage.ResultsIn our study population of 1230 invasive EOC cases (558 non-Hispanic White, 74 non-Hispanic Black, 73 Asian, 30 Pacific Islander and 36 Hispanic cases), 63% of the women died (all-cause death) after a mean = 4.8 years (SD = 4.1) of follow-up following diagnosis. Compared with non-Hispanic White cases, Asian cases had better overall survival, HR = 0.76 (95% CI = 0.58–0.98), whereas there were no differences in survival for other racial and ethnic groups.ConclusionsThese findings highlight the need to investigate how differences in access to healthcare may influence observed racial and ethnic disparities for EOC.

Abstract B089: Understanding the relationship between neighborhood disorder, racial segregation, and ovarian cancer survival in African American women

Abstract Black women have a 10% lower 5-year survival of epithelial ovarian cancer (EOC) than White women, despite having a 25% lower incidence of OC than White women. Evidence suggests that these health disparities can be partially explained by neighborhood social and environmental factors such as disorder. We used Google Street View (GSV) imagery to estimate a measure of neighborhood disorder (ND) at the block group level within the largest multi-state cohort study of Black women diagnosed with EOC (AACES) between 2010 and 2015. 592 AACES participants were enrolled and geocoded residing in 544 unique block groups. We used the online Computer Assisted Neighborhood Visual Assessment System (CANVAS), to conduct virtual audits at 5 street address locations in each block group. These audits included questions related to the presence of different types of land use, the quality of the built structures, and the presence of other markers of ND. Factor analysis identified 5 distinct neighborhood factors: developmental intensity, development age, neighborhood disorder, land use, and green/blue space. An ND score was calculated for each block group audited based on the ND factor, which included the condition of residential units and yards, and assigned to the residents of that block group. Initial analyses indicated that this score did not impact EOC survival. We conducted Weibull AFT survival analyses with frailty to assess the impact of racial segregation on the relationship between ND and EOC survival. An Isolation Index was calculated to quantify the segregation of non-Hispanic Blacks compared to other racial groups. Increased racial isolation was associated with decreased survival (HR: 1.234, 95%CI: 1.03-1.60), after adjustment. Additionally, to understand the impact of the social aspects of disadvantage compared to the built aspects of our disorder score, we examined ADI as a predictor of EOC survival. Increasing ADI was associated with marginally decreased survival (HR: 1.002, 95%CI: 1.00-1.01), after adjustment. The lack of association between our disorder score and EOC survival and the presence of an association between the measures of racial isolation and ADI and EOC survival could indicate that it is the social aspects of an environment, not the built factors, that are driving EOC survival. Future research should explore the impacts of racial segregation and individual-level perceived racism on EOC survival. Citation Format: Christopher Pierson, Steve J. Mooney, Andrew B. Lawson, Joellen M. Schildkraut, Edward S. Peters. Understanding the relationship between neighborhood disorder, racial segregation, and ovarian cancer survival in African American women [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 B089.

NLRP12 is a prognostic biomarker and correlated with immune infiltrates in epithelial ovarian cancer.

NLRP12 is a member of the intracellular Nod-like receptor (NLR) family, suggesting it is an innate immune receptor for the initiation and progression of several cancers. However, its role on prognosis and immune infiltrates in epithelial ovarian cancer (EOC) is still unknown. The present study aimed to evaluate its prognostic value and its association with immune infiltrates in EOC. The mRNA expression of NLRP12 of EOC from The Cancer Genome Atlas (TCGA) was analyzed. The association between NLRP12 and clinicopathological characters was evaluated with logistic regression. The association between NLRP12 expression and survival was analyzed by Cox regression and Kaplan-Meier analyses. A nomogram was used to predict the impact of NLRP12 on prognosis. Gene Ontology term analysis and gene set enrichment analysis (GSEA) were performed to identify the signaling pathways related to NLRP12 expression. Immune cells infiltration for NLRP12 was analyzed using single-sample GSEA. The relationship between NLRP12 and tumor-infiltrating immune cells (TICs) was investigated by a Wilcoxon rank sum test. The expression of NLRP12 were also further verified in EOC tissues and cell lines. Additionally, we confirmed the biological function of NLRP12 in vitro. NLRP12 was highly expressed in patients with EOC from TCGA. High NLRP12 expression correlated with poor disease-specific survival (p < 0.001) and overall survival (p < 0.001). Multivariate analysis revealed that NLRP12 expression was an independent prognostic marker for overall survival (p = 0.042). The C-indexes and calibration plots of the nomogram based on multivariate analysis indicated an effective predictive performance for EOC patients. GSEA showed enrichment of cell adhesion, tumorigenesis and immune response in the NLRP12 high expression group. Increased NLRP12 expression correlated positively with several TICs, including macrophages, neutrophils, T effector memory cells and immature dendritic cells (p < 0.001). In addition, NLRP12 silencing inhibited cell proliferation and migration in EOC cells. In conclusion, increased NLRP12 expression correlated significantly with poor survival and immune infiltration in EOC.

Impact of postoperative residual disease on survival in epithelial ovarian cancer with consideration of recent frontline treatment advances: A systematic review and meta-analysis

BackgroundCurrent treatment strategies for primary epithelial ovarian cancer (EOC) have significantly evolved, and the value of complete cytoreduction has not yet been reassessed. The study aimed to investigate the impact of residual disease after cytoreductive surgery for EOC on survival outcomes within the recent paradigm of frontline ovarian cancer treatment. MethodsWe searched relevant literature from the MEDLINE, Embase, and Cochrane Library databases to identify randomized controlled trials and prospective clinical trials of primary EOC published between 1 January 2000 and 22 September 2022. To evaluate the impact of postoperative residual tumors on progression-free survival (PFS) and OS, we constructed a linear regression model for log-transformed median PFS and OS. Patients who did or did not receive first-line maintenance therapy were examined. ResultsA total of 97 trials with 43,260 patients were included:2476 received poly(ADP-ribose) polymerase (PARP) inhibitors and 6587 received bevacizumab. Multivariable analysis of the linear regression model of all studies revealed that the median OS increased by 12.97% for every 10% increase in complete cytoreduction rates, independent of the use of systemic maintenance. In the subgroup analysis of patients receiving maintenance therapies, the effect of complete tumor clearance was potentiated, with a median OS increase of 19.13% for every 10% increase in complete cytoreduction rates. ConclusionTotal macroscopic tumor clearance at the initial presentation of EOC significantly prolongs OS. Our results establish the importance of complete surgical cytoreduction, even after the introduction of recent advances in frontline treatment for EOC.

Prognostic Factors and a Predictive Nomogram of Cancer-Specific Survival of Epithelial Ovarian Cancer Patients with Pelvic Exenteration Treatment.

The aim of this study was to explore prognostic factors, develop and internally validate a prognostic nomogram model, and predict the cancer-specific survival (CCS) of epithelial ovarian cancer (EOC) patients with pelvic exenteration (PE) treatment. A total of 454 EOC patients from the Surveillance, Epidemiology, and End Results (SEER) database were collected according to the inclusion criteria and randomly divided into the training (n = 317) and validation (n = 137) cohorts. Prognostic factors of EOC patients with PE treatment were explored by univariate and multivariate stepwise Cox regression analyses. A predictive nomogram was constructed based on selected risk factors. The predictive power of the constructed nomogram was assessed by the time-dependent receiver operating characteristic (ROC) curve. Kaplan-Meier (KM) curve stratified by patients' nomoscore was also plotted to assess the risk stratification of the established nomogram. In internal validation, the C index, calibration curve, and decision curve analysis (DCA) were employed to assess the discrimination, calibration, and clinical utility of the models, respectively. In the training cohort, age, histological type, Federation of Gynecology and Obstetrics (FIGO) stage, number of examined lymph nodes, and number of positive lymph nodes were found to be independent prognostic factors of postoperative CSS. A practical nomogram model of EOC patients with PE treatment was constructed based on these selected risk factors. Time-dependent ROC curves and KM curves showed the superior predictive capability and excellent clinical stratification of the nomogram in both training and validation cohorts. In the internal validation, the C index, calibration plots, and DCA in the training and validation cohorts confirmed that the nomogram presents a high level of prediction accuracy and clinical applicability. Our nomogram exhibited satisfactory survival prediction and prognostic discrimination. It is a user-friendly tool with high clinical pragmatism for estimating prognosis and guiding the long-term management of EOC patients with PE treatment.

Estimation Recurrence Free Survival of the Epithelial Ovarian Cancer Using Classification and Regression Tree

Background: Epithelial ovarian cancer is one of the leading causes of death from gynecological cancers in the Western world. One of the important objectives of medical research is to determine predictors of an event. Regarding the interaction of risk factors, regression methods are unsuitable when the number of factors is high. Objectives: Regarding frequency predictors of recurrence-free survival in epithelial ovarian cancer, our aim in this article is to determine predictors and time to first recurrence using a classification and regression tree model. Methods: This retrospective analysis used medical and chemotherapy records of 141 patients with epithelial ovarian cancer between 2007 and 2018. They were referred to Imam Hossein Hospital in Tehran. Data were analyzed using classification and regression trees in Rver3.4.3. Results: The regression tree results showed that the worst recurrence-free survival in metastatic patients was in grade II patients (15.03 ± 11 months), but in patients without metastases were in patients with CA125 tumor marker above 207 that used 3-week chemotherapy courses (14.53 ± 6.4 months). The classification tree also showed that the most probability of the first recurrence in metastatic patients was in patients with adjuvant chemotherapy (0.81), and patients without metastases were among those with stages 2, 3, and 4 with the maximum platelet count above 305,000 and less than 35 years old (0.75). Conclusions: The classification and regression tree models, without any assumptions, can estimate the probability of recurrence in different subgroups. These models can be used in deciding due to the ease of interpretation by physicians and paramedics.