Uncovering the Role of <i>ALDH1A2</i> 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 <i>aldehyde dehydrogenase 1</i> (<i>ALDH1</i>) gene family is involved in cellular detoxification and biosynthetic processes and has been implicated in various cancers. This study investigated the association between the <i>ALDH1</i> family members and prostate cancer recurrence. We conducted a two-stage genetic association study involving 134 single-nucleotide polymorphisms within the <i>ALDH1</i> 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. <i>ALDH1A2</i> rs16939929 showed a robust association with BCR-free survival in both discovery and replication cohorts. Functional analyses indicated that rs16939929 affected <i>ALDH1A2</i> expression in various tissues. Pooled analysis of 42 prostate cancer gene expression datasets revealed that <i>ALDH1A2</i> expression was significantly lower in prostate cancer tissues and higher expression was associated with better patient prognosis. Enrichment analyses revealed that <i>ALDH1A2</i> 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, <i>ALDH1A2</i> expression was associated with increased immune cell infiltration into the prostate cancer microenvironment. In conclusion, <i>ALDH1A2</i> rs16939929 is a significant predictor of BCR-free survival in prostate cancer, potentially through its effects on the gene expressions of <i>ALDH1A2</i> and cell adhesion molecules. These findings suggest that <i>ALDH1A2</i> plays a tumor-suppressive role in prostate cancer progression.