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ARTICLE

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

Kyungeun Kim1,2,#, Eunho Cho3,#, Eun Joo Chung4, Kwon-Ho Song5, Tae Woo Kim3,6, Seoung Wan Chae1,*, Joon-Yong Chung7,*
1 Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
2 Pathology Center, Seegene Medical Foundation, Seoul, Republic of Korea
3 Department of Convergence Medicine, College of Medicine, Korea University, Seoul, Republic of Korea
4 Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
5 Department of Cell Biology, Daegu Catholic University School of Medicine, Daegu, Republic of Korea
6 BK21 Graduate Program, Department of Biomedical Science, Korea University College of Medicine, Seoul, Republic of Korea
7 Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
* Corresponding Author: Seoung Wan Chae. Email: email; Joon-Yong Chung. Email: email
# These authors contributed equally to this work
(This article belongs to the Special Issue: Novel Biomarkers and Treatment Strategies in Solid Tumor Diagnosis, Progression, and Prognosis (Ⅱ))

Oncology Research https://doi.org/10.32604/or.2026.083437

Received 03 April 2026; Accepted 25 June 2026; Published online 27 July 2026

Abstract

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.

Keywords

Gastric cancer; peptidyl-prolyl isomerase B; cyclophilin B; prognostic biomarker; tumorigenicity

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