Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
Characteristics and prognosis of primary gastric adenosquamous carcinoma: A multicenter retrospective study based on propensity score matching
Yi-Wen Chen, Zhong-Yi Dong, Xin-Xin Wang, Yi Cao, Jian-Xian Lin, Hao Chen, Hao-Yu Zhang, Yong-Biao Xiao, Guo-Xin Li, Zheng-Rong Li, Lin Chen, Xiang Xia, Zi-Zhen Zhang
Yi-Wen Chen, Zhong-Yi Dong, Hao-Yu Zhang, Xiang Xia, Department of Gastrointestinal Surgery, Renji Hospital, Shanghai 200127, China
Xin-Xin Wang, Lin Chen, Department of General Surgery, First Medical Centre of Chinese PLA General Hospital, Beijing 100853, China
Yi Cao, Zheng-Rong Li, Department of Gastrointestinal Surgery, The First Affiliated Hospital, Nanchang University, Nanchang 330006, Jiangxi Province, China
Jian-Xian Lin, Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou 35000, Fujian Province, China
Hao Chen, Division of Gastrointestinal Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Yong-Biao Xiao, Department of Gastrointestinal Surgery, The First People’s Hospital of Kashgar, Kashgar 844000, Xinjiang Uygur Autonomous Region, China
Guo-Xin Li, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Zi-Zhen Zhang, Department of Gastrointestinal Surgery, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Co-first authors: Yi-Wen Chen and Zhong-Yi Dong.
Co-corresponding authors: Xiang Xia and Zi-Zhen Zhang.
Author contributions: Zhang ZZ, Xia X, Chen L, Zheng CH, Li ZR, and Li GX designed the research study; Chen YW and Dong ZY performed the research, analyzed the data, and wrote the manuscript; Wang XX, Cao Y, Lin JX, Chen H, Zhang HY, and Xiao YB collected the data and provided clinical resources; all authors read and approved the final manuscript; Zhang ZZ had full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis; Chen YW and Dong ZY contributed equally to this work as co-first authors; both authors played critical roles in the acquisition of multicenter clinical data, performed the propensity score matching and statistical analysis, and collaborated closely on drafting and revising the manuscript; Zhang ZZ and Xia X contributed equally to this work as co-corresponding authors; the authors jointly conceptualized the study design, secured funding support, and supervised the entire research process and were responsible for the final review and critical revision of the manuscript for important intellectual content.
Supported by the Science and Technology Commission of Shanghai Municipality, No. 25SF1905600; and National Natural Science Foundation of China, No. 82303428, No. 82473077 and No. 82473065.
Institutional review board statement: This study was approved by the Ethics Committee of the Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (approval No. KY2022-084-B).
Informed consent statement: The need for informed consent was waived by the Ethics Committee of Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine because of the retrospective nature of the study.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: All data generated during this study are included in this published article/
Supplementary material. The anonymized raw data that support the findings of this study are available from the corresponding author upon reasonable request.
Corresponding author: Zi-Zhen Zhang, MD, Professor, Department of Gastrointestinal Surgery, School of Medicine, Shanghai Jiao Tong University, No. 160 Pu Jian Road, Shanghai 200127, China.
zhangzizhen@renji.com
Received: December 11, 2025
Revised: January 12, 2026
Accepted: February 24, 2026
Published online: May 15, 2026
Processing time: 154 Days and 23.9 Hours
BACKGROUND
Primary gastric adenosquamous carcinoma (PGASC) is a rare malignancy with a poor prognosis. The current clinical understanding of PGASC has been derived from Western populations and may not accurately reflect the disease characteristics of Eastern populations. Furthermore, the efficacy of standard adjuvant chemotherapy for the treatment of PGASC has not been determined.
AIM
To explore the clinicopathological features, prognosis, and chemotherapy efficacy of PGASC in a Chinese cohort.
METHODS
This retrospective analysis of 108 patients with PGASC was conducted from March 2007 to December 2021 at six medical centers in China. The data from these patients was compared with the data from 468 randomly selected patients with pathologically diagnosed gastric adenocarcinoma (GAC) from the same time period at Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. The characteristics, prognosis, and chemotherapy efficacy were investigated by propensity score matching.
RESULTS
Patients with PGASC had higher rates of tumors located in the cardia (44.4% vs 22.9%), lymphovascular invasion (55.6% vs 35.5%), and perineural invasion (50.0% vs 32.7%) than patients with GAC. Immunohistochemical analysis revealed that the PGASC group had a significantly higher proportion of cells, with at least 10% expressing programmed cell death-ligand than the GAC group (13.2% vs 2.8%; P < 0.001). Patients with PGASC had significantly poorer 5-year overall survival rates compared with patients with GAC (16.6% vs 49.3%, P < 0.001). In the PGASC group overall survival was similar in patients who received chemotherapy and those who did not.
CONCLUSION
PGASC has different characteristics than GAC, including a more aggressive presentation, a poorer prognosis, and higher programmed cell death-ligand 1 expression.
Core Tip: This multicenter retrospective study represents the largest Eastern cohort of patients with primary gastric adenosquamous carcinoma (PGASC). Applying propensity score matching to patients with gastric adenocarcinoma to investigate PGASC we found that PGASC was associated with worse prognosis. No survival benefit was observed for standard adjuvant chemotherapy in locally advanced cases. However, increased programmed cell death-ligand 1 expression was observed in PGASC tissues, indicating that immunotherapy could represent a promising novel therapeutic strategy for this aggressive malignancy.
