Uncovering the Role of in Prostate Cancer: Insights from Genetic and Expression Analyses.

Biochemical recurrence (BCR) is a critical concern in prostate cancer management; however, its underlying genetic determinants remain poorly understood. The () gene family is involved in cellular detoxification and biosynthetic processes and has been implicated in various cancers. This study investigated the association between the family members and prostate cancer recurrence. We conducted a two-stage genetic association study involving 134 single-nucleotide polymorphisms within the family to assess their association with BCR-free survival in prostate cancer. Gene set and pathway enrichment analyses were performed to explore the biological relevance of significant genes across multiple datasets. rs16939929 showed a robust association with BCR-free survival in both discovery and replication cohorts. Functional analyses indicated that rs16939929 affected expression in various tissues. Pooled analysis of 42 prostate cancer gene expression datasets revealed that expression was significantly lower in prostate cancer tissues and higher expression was associated with better patient prognosis. Enrichment analyses revealed that was co-expressed with genes primarily involved in cell adhesion pathways. Further analysis confirmed that several of these co-expressed cell adhesion molecules were associated with improved patient survival. In addition, expression was associated with increased immune cell infiltration into the prostate cancer microenvironment. In conclusion, rs16939929 is a significant predictor of BCR-free survival in prostate cancer, potentially through its effects on the gene expressions of and cell adhesion molecules. These findings suggest that plays a tumor-suppressive role in prostate cancer progression.