Prognostic impact and racial disparities of chromosome 8q gains in prostate cancer: Insights from integrated molecular profiling.

Abstract

e17121 Background: Chromosome arm 8q is frequently amplified in prostate cancer, harboring genes that drive tumor progression, therapy resistance, and poor outcomes. Key loci include MYC , which regulates cell proliferation; AR , central to prostate cancer biology and resistance; and RAD21 , essential for chromosomal stability. While the prognostic implications of 8q gains have been explored, their role in driving racial disparities in prostate cancer outcomes remains underexplored. This study investigates chromosome 8q amplification as a prognostic biomarker, examining its differential prevalence and impact across racial groups to elucidate its contribution to disparities in disease progression and patient survival. Methods: Using cBioPortal's clinical and genomic data from Memorial Sloan Kettering Cancer Center, this work examined two datasets from 2021 and 2024. Comprehensive genomic profiling included copy number alterations, mutational co-occurrence of important 8q genes, and mutational analysis. Multivariate Cox regression and Kaplan-Meier survival analysis were conducted to evaluate the impact of 8q amplifications on overall survival (OS) and disease outcomes, stratified by racial demographic groups and disease stages. Results: In this cohort of 1,577 prostate cancer patients, 652 (41%) exhibited chromosome 8q amplification, which correlated with aggressive tumor phenotypes. The most common amplifications were observed in PTEN (21%), FOXA1 (17%), AR (16%), and MYC (7%),, with notable co-occurrences observed between MYC-RAD21, MYC-NBN, and PRDM14-ELOC ( P = <0.001), linking these alterations to genomic instability. Kaplan-Meier analysis showed patients with 8q gain had significantly inferior overall survival (HR = 2.31, 95% CI: 1.99 - 2.69, P < 0.001, mOS gain vs neutral: 35mo vs 55mo). Black patients exhibited a higher frequency of 8q gain (10% vs. 6.1%, P = 0.003) and distinct oncogenic profiles, including MYC (12%), RAD21 (7%), and LYN (4%) alterations. While Black patients experienced inferior overall outcomes, chromosome 8q amplification was a consistent predictor of poor prognosis across all racial groups. Conclusions: This study establishes chromosome 8q amplification as a robust prognostic biomarker in prostate cancer. The integration of clinical and genomic data highlights the potential of 8q amplification to guide personalized therapeutic strategies. These findings underscore the value of incorporating 8q analysis into clinical risk stratification frameworks to enhance treatment decision-making and address racial disparities in prostate cancer outcomes.