Copyright
©The Author(s) 2026. Published by Baishideng Publishing Group Inc. All rights reserved.
High PD-L1 expression as a negative prognostic factor in stage III but not in stage II gastric cancer
Hui-Min Zhang, Feng-Ping Li, Heng-Yi Zhang, Xin-Ru Liu, Xin-Hua Chen, Hua-Yuan Liang, Xiao Yan, Qing Xie, Rou Zhong, Min Lai, Xue-Feng Zhong, Hao Liu, Li-Ying Zhao
Hui-Min Zhang, Heng-Yi Zhang, Xin-Ru Liu, Xiao Yan, Qing Xie, Rou Zhong, Min Lai, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Feng-Ping Li, Xin-Hua Chen, Hao Liu, Li-Ying Zhao, Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Hua-Yuan Liang, Department of Gastrointestinal Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
Xue-Feng Zhong, Department of the Medical, 3D Medicines Inc., Shanghai 201321, China
Co-first authors: Hui-Min Zhang and Feng-Ping Li.
Co-corresponding authors: Hao Liu and Li-Ying Zhao.
Author contributions: Zhang HM and Li FP contributed equally to this study as co-first authors; Liu H and Zhao LY contributed equally to this study as co-corresponding authors; Liu H and Zhao LY conceptualized the research; Zhang HM, Li FP, and Zhang HY conducted the formal analysis; Zhao LY provided the funding support; all authors contributed to data curation and investigation; Liang HY, Liu XR, Yan X, and Xie Q contributed to the methodology; Liu H and Zhao LY managed the project; Zhang HM, Li FP, and Zhong XF utilized the software; Chen XH, Liu H, and Zhao LY supervised the research; Zhang HM, Liu XR, and Lai M validated the results; Li FP, Zhong R, and Zhang HY handled the visualization; Zhang HM and Li FP wrote the original draft; all authors reviewed and edited the manuscript.
Supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project, No. 2023ZD0501500.
Institutional review board statement: The study was reviewed and approved by the Clinical Research Ethics Committee of Nanfang Hospital, Southern Medical University (Approval No. NFEC-2025-476).
Informed consent statement: Informed consent was waived by the Clinical Research Ethics Committee of Nanfang Hospital, Southern Medical University.
Conflict-of-interest statement: The authors declare that the paper was carried out without any commercial or financial relationships that could be construed as a potential conflict of interest.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Data sharing statement: The raw data supporting the conclusions of this article will be accessible from the authors, without undue reservation.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Li-Ying Zhao, MD, PhD, Assistant Professor, Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Ave. North, Guangzhou 510515, Guangdong Province, China.
zlyblue11@163.com
Received: October 21, 2025
Revised: December 8, 2025
Accepted: January 4, 2026
Published online: February 28, 2026
Processing time: 114 Days and 4 Hours
BACKGROUND
The prognostic value of programmed death ligand-1 (PD-L1) expression in patients with gastric or gastroesophageal junction cancer (G/GEJC) at different stages remains unclear. We hypothesized that high PD-L1 expression is associated with poor survival in patients with pathological stage III (pIII) G/GEJC.
AIM
To investigate the relation between PD-L1 expression and survival outcomes in patients with pathological stage II (pII)-pIII G/GEJC.
METHODS
In this retrospective cohort study, we collected the clinicopathological data of 388 consecutive patients with pII/pIII G/GEJC who underwent gastrectomy without neoadjuvant therapy at Nanfang Hospital, Southern Medical University. Postoperative tissue samples were collected to evaluate PD-L1 expression. Combined positive score (CPS) ≥ 1 was defined as PD-L1-positive, and CPS ≥ 5 as high PD-L1 expression. Survival outcomes were analyzed using Kaplan-Meier and Cox proportional hazards models.
RESULTS
In pII G/GEJC, no significant differences were found in 3-year disease-free survival (DFS; 88.5% vs 87.9%, P = 0.939) or 3-year overall survival (OS; 92.3% vs 89.9%, P = 0.621) between PD-L1-positive and PD-L1-negative groups or between high and low PD-L1 expression groups (3-year DFS: 91.8% vs 84.2%, P = 0.138; 3-year OS: 94.2% vs 88.4%, P = 0.233). In pIII G/GEJC, PD-L1-positive patients had poorer 3-year DFS (52.2% vs 67.8%, P = 0.030) and 3-year OS (65.1% vs 78.2%, P = 0.007) than PD-L1-negative patients. High PD-L1 expression was associated with significantly inferior 3-year DFS (50.2% vs 64.8%, P = 0.023) and 3-year OS (64.0% vs 75.1%, P = 0.036) compared to low PD-L1 expression. Multivariate analysis revealed that high PD-L1 expression was independently associated with shorter DFS (HR = 1.624, P = 0.027) and OS (HR = 1.653, P = 0.043) in patients with pIII G/GEJC. Sensitivity analyses confirmed the robustness of the OS findings.
CONCLUSION
High PD-L1 expression serves as an independent adverse prognostic biomarker in stage III but not stage II G/GEJC. These findings indicate a stage-dependent prognostic value of PD-L1 expression in G/GEJC.
Core Tip: This retrospective cohort study revealed that high programmed death ligand-1 (PD-L1) expression was an independent adverse prognostic factor for disease-free and overall survival in pathological stage III gastric or gastroesophageal junction cancer (G/GEJC). However, in pathological stage II G/GEJC, patients with high PD-L1 expression tended to have better survival despite the lack of statistical significance. These findings align with the subgroup analysis of the KEYNOTE-585 trial, which indicated the clinical benefit of anti-programmed death 1 therapy in stage III G/GEJC but not in stage II. This study provides theoretical support for designing future perioperative precision immunotherapy trials in G/GEJC.
