Prognostic Significance of -Related Gene Variants in Patients With Prostate Cancer Undergoing Androgen Deprivation Therapy.

BACKGROUND/AIM: Prostate cancer remains a major global health burden, with treatment resistance posing a significant challenge. Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), a histone methyltransferase, is frequently overexpressed in prostate cancer, contributing to tumor progression and castration resistance. Clinical trials of EZH2 inhibitors may have therapeutic benefits. This study aimed to evaluate the impact of genetic variants in -related genes on survival outcomes in prostate cancer.

PATIENTS AND METHODS

We conducted a genetic association study evaluating 76 single nucleotide polymorphisms (SNPs) across 10 -related genes in 630 patients with prostate cancer undergoing androgen deprivation therapy (ADT). Functional analyses, including gene ontology and pathway enrichment assessments, were performed to elucidate the biological significance of key genes across multiple datasets.

RESULTS

rs77993651 was significantly associated with both cancer-specific survival [hazard ratio (HR)=0.82, =0.042] and overall survival (HR=0.80, =0.011). Functional annotation indicated that rs77993651 resides within enhancer histone marks, potentially regulating expression. Elevated expression was observed in prostate tumor tissues and correlated with more aggressive features and shorter progression-free survival. Gene set enrichment analysis revealed that expression was strongly associated with cell cycle G/M checkpoint regulation, implicating a role in prostate cancer progression.

CONCLUSION

The prognostic significance of and its genetic variant rs77993651 in prostate cancer is herein highlighted. Targeting -mediated pathways may offer novel therapeutic strategies for prostate cancer management.