Prognostic Significance and Functional Role of PPIB in a Retrospective Cohort of Patients with Advanced Gastric Cancer.

Objectives: Gastric cancer remains a major global health burden, and robust biomarkers are needed to improve risk stratification. Although peptidyl-prolyl isomerase B (PPIB) has been suggested as a potential oncogenic factor, its clinical utility in gastric cancer remains unclear. This study aims to evaluate the clinicopathological and prognostic significance of PPIB mRNA expression and delineate its functional role in driving tumor progression. Methods: PPIB mRNA expression was evaluated in a retrospective cohort of 497 gastric cancer patients using RNAscope in situ hybridization and digital image analysis. Functional roles and underlying mechanism were assessed through siRNA-mediated knockdown, plasmid-driven overexpression, and STAT3-targeted rescue experiments in vitro. Results: High PPIB expression was significantly associated with aggressive clinicopathological features, including larger tumor size, advanced T stage, and lymph node metastasis. Patients with high PPIB expression had significantly worse progression-free survival (PFS) and overall survival (OS) compared to those with low expression, particularly in advanced stage. Multivariate analysis identified high PPIB expression as an independent predictor of poor PFS and OS. Functionally, PPIB silencing suppressed gastric cancer cell proliferation, migration, and invasion, whereas its overexpression enhanced these oncogenic behaviors in both cancerous and non-tumorigenic cells. These aggressive phenotypes were effectively mitigated through STAT3 targeted functional rescue experiments. Conclusions: PPIB is a robust independent prognostic biomarker for gastric cancer, especially in advanced stages. Its role in driving aggressive phenotypes via STAT3 signaling underscore its potential for risk stratification and as a therapeutic target.