Prognostic Significance of PPFIA2 in Localized Prostate Cancer: Integrative Analysis and Functional Validation

Prostate cancer (PCa) is a leading malignancy in men, with biochemical recurrence (BCR) indicating potential disease progression in up to 50% of patient's post-curative therapy. The liprin-α family gene PPFIA2 has emerged as a potential biomarker in PCa, yet its prognostic role in localized disease remains underexplored.

PPFIA2 expression was analyzed using high throughput data from TCGA-PRAD, CPC, Stockholm, and GSE54460 cohorts, with validation in an in-house cohort via immunohistochemistry (IHC). Kaplan-Meier and Cox regression analyses assessed its prognostic value for BCR and overall survival. In vitro, PPFIA2 knockdown effects were evaluated in LNCaP and C4-2 cell lines using CCK-8 and Transwell assays. Gene Set Enrichment Analysis (GSEA) explored biological pathways, and mutation profiles were analyzed using maftools.

High PPFIA2 expression was associated with earlier BCR across multiple cohorts. IHC confirmed elevated PPFIA2 protein levels in PCa tissues, correlating with poorer prognosis. PPFIA2 knockdown reduced proliferation and migration in PCa cell lines. GSEA revealed PPFIA2's activation of proliferation-related pathways and suppression of protein synthesis. High PPFIA2 expression was linked to a lower SPOP mutation frequency.

PPFIA2 is an unfavorable prognostic biomarker for localized PCa. Its oncogene effect highlights its potential for risk stratification and targeted therapy.