Abstract C006: Identifying aggressive prostate cancer variants toward reducing cancer disparities

Abstract

Abstract Background: Prostate cancer (PrCa) has a more detrimental impact on Black men than on men from other races, owing to factors such as limited screening, inadequate treatment received, low involvement in clinical research, and a history of unfair treatment in the healthcare system, among others. Patients with PrCa have a dismal prognosis and are often detected using biomarkers like the prostate-specific antigen (PSA) test and tumor staging. In localized PrCa, there are not enough biomarkers for diagnosis and prognosis. Genomic databases, such as the cBioPortal, may be utilized to conduct studies, evaluate information, discuss findings, and forecast next-generation solutions for effectively combating the increasing prevalence and mortality rates of PrCa. Method: The cBioPortal, containing around 10,366 samples from 22 studies, was explored to identify genomic alterations in genes. We filtered through the datasets and chose prostate adenocarcinoma (MSK, Clin Cancer Res. 2022) and race differences in prostate cancer (MSK, 2021). A total of 3,486 PrCa patients were included in our study but used 1,809 patients. Whereas 1,677 patients were eliminated due to sample types ("not available” NA), race (only black (n= 152) and white (n= 1,657) were included), and sex (males). Primary prostate cancers (n = 994) and metastatic prostate cancers (n = 815) were the two categories of PrCa samples studied. After merging the query results from the two datasets, we identified and estimated the numbers and percentages of overall gene alterations and individual categories of gene alterations. Results: We calculated the prevalence of reported alterations (i.e., mutations, copy number alterations (CNAs), and structural variants) in 10 genes: FOXA1 (AR pathway), TP53, ERG, TMPRSS2 (ETS signaling), PTEN (PI3K-AKT-mTOR signaling), CDK12, KMT2C and BRCA2 (DNA damage repair), SPOP, and MYC (down-regulated by androgen). MYC, FOXA1, SPOP, CDK12, KMT2C, and AR exhibit higher overexpression frequencies in black males than in white men in the profiled samples (P < 0.05). MYC overexpression was observed to be more prevalent in PrCa samples from black patients than samples from white patients, and statistical significance was achieved (9.2% vs 5.6%, p < 0.05). Similarly, black patients had higher levels of PTEN expression than white patients, albeit statistical significance was not achieved (24.0% vs 14.5%, p = 0.08). FOXA1 overexpression is higher in blacks than whites (17.7% vs 15.5%, p = 0.27). CDK12 and KMT2C genomic alterations are more prevalent in black patients than in white patients (60.8% vs 29.8%; 9.9% vs 5.7%, p < 0.05). Using the chi-square (for the racial category and smoking status) and Wilcoxon (for age at diagnosis) statistical tests, clinical factors varied significantly (p<0.001). Conclusion: It is important to understand the genetic underpinnings of disparities in prostate cancer. Our findings support a modest association between genomic alterations in PrCa genes and differential expression by race. Citation Format: Olumide Arigbede, Opeyemi Ogungbola, Sarah Buxbaum, Sara Falzarano, Suhn Rhie. Identifying aggressive prostate cancer variants toward reducing cancer disparities [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 C006.