Divergent effects of PLA2G7 on prostate cancer biochemical recurrence in European American and African American men

BACKGROUND: Identification and characterization of prostate tumor markers differentially expressed in European American (EA) men vs African American (AA) men has been one of the focus areas positioned to understand and address prostate cancer disparity in the US. Whereas some genes are differentially expressed, validation studies are limited, and the impact of these expression differences on recurrence risk remains unclear. METHODS: This study focused on phospholipase A2 group 7 (PLA2G7) in prostate cancer surgical specimens from EA and AA patients. A nested case-control study was conducted to evaluate the prognostic value of the PLA2G7 protein while controlling for age, stage, and Gleason, followed by re-analysis of a published dataset of 556 EA and 596 AA prostate cancer patients. Expression signatures correlated with PLA2G7 were investigated in both patient populations. RESULTS: PLA2G7 was more frequently overexpressed in EA tumors than AA tumors, and higher tumor-specific PLA2G7 expression was associated with divergent outcomes: lower biochemical recurrence risk in EA men but elevated risk in AA men. Expression in noncancer tissues showed no prognostic value. Whereas androgen response signatures were consistently enriched in high-PLA2G7 tumors across both groups, immune and inflammatory response gene sets showed opposite enrichment trends between AA and EA men. CONCLUSION: This study represents the first identification and validation of a tumor-specific marker that is both differentially expressed between prostate cancers in AA and EA men and demonstrates opposite prognostic effects based on self-reported race/ethnicity. The findings emphasize the importance of evaluating prostate tumor markers across diverse geographic ancestries.