Pu WF, Yang X, Wang XQ, Guo XG, Yang MY. Stemness signatures reflect prognostic disturbances in gastric cancer. World J Gastrointest Oncol 2025; 17(7): 107211 [DOI: 10.4251/wjgo.v17.i7.107211]
Corresponding Author of This Article
Wen-Feng Pu, Department of Gastroenterology, Beijing Anzhen Nanchong Hospital of Capital Medical University and Nanchong Central Hospital, No. 97 Renmin South Road, Shunqing District, Nanchong 637000, Sichuan Province, China. 1047951869@qq.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Jul 15, 2025; 17(7): 107211 Published online Jul 15, 2025. doi: 10.4251/wjgo.v17.i7.107211
Stemness signatures reflect prognostic disturbances in gastric cancer
Wen-Feng Pu, Xiao Yang, Xiao-Qing Wang, Xiao-Guang Guo, Mi-Yuan Yang
Wen-Feng Pu, Department of Gastroenterology, Beijing Anzhen Nanchong Hospital of Capital Medical University and Nanchong Central Hospital, Nanchong 637000, Sichuan Province, China
Xiao Yang, College of Pharmacy, Chongqing Medical University, Chongqing 400000, China
Xiao-Qing Wang, Department of Nuclear Medicine, Beijing Anzhen Nanchong Hospital of Capital Medical University and Nanchong Central Hospital, Nanchong 637000, Sichuan Province, China
Xiao-Guang Guo, Department of Pathology, Beijing Anzhen Nanchong Hospital of Capital Medical University and Nanchong Central Hospital, Nanchong 637000, Sichuan Province, China
Mi-Yuan Yang, Department of Clinical Laboratory, Beijing Anzhen Nanchong Hospital of Capital Medical University and Nanchong Central Hospital, Nanchong 637000, Sichuan Province, China
Co-first authors: Wen-Feng Pu and Xiao Yang.
Author contributions: Pu WF is the primary and corresponding author of the paper; Yang X also contributed equally to this work and shares the role of the corresponding author; PU WF oversaw and coordinated the project; Pu WF and Yang X were responsible for conducting the experiments, analyzing the data, and drafting the manuscript; Wang XQ and Guo XG were involved in data curation and assisted with the behavioral experiments; Yang MY provided additional resources; Guo XG handled the pathological processing and immunohistochemistry analysis; Yang X also played a key role in data collection and validation.
Institutional review board statement: This study was approved by the Ethics Committee of Nanchong Central Hospital, Approval No: 2024 No. 113.
Conflict-of-interest statement: The authors state that no commercial or financial relationships could be viewed as potential conflicts of interest during this research.
Data sharing statement: The processed scRNA-seq data and the codes associated with this study are available in Zenodo (https://doi.org/10.5281/zenodo.15004451).
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: Wen-Feng Pu, Department of Gastroenterology, Beijing Anzhen Nanchong Hospital of Capital Medical University and Nanchong Central Hospital, No. 97 Renmin South Road, Shunqing District, Nanchong 637000, Sichuan Province, China. 1047951869@qq.com
Received: March 19, 2025 Revised: April 20, 2025 Accepted: May 22, 2025 Published online: July 15, 2025 Processing time: 117 Days and 23.5 Hours
Abstract
BACKGROUND
Tumors characterized by high cellular stemness often have unfavorable clinical outcomes, primarily due to their heightened potential for metastasis and resistance to chemotherapy. Among the model genes, the clinical relevance and prognostic significance of Niemann-Pick type C2 (NPC2) in gastric cancer (GC) remained largely unexplored.
AIM
To identify stemness-associated genes in GC.
METHODS
In this study, epithelial cells were categorized as either tumor or normal epithelial cells using the infer copy number variation method. Stemness scores were calculated for both cell types. The hierarchical Weighted Gene Co-expression Network Analysis identified two gene modules with the strongest association with stemness. Prognostically significant stemness-related genes were pinpointed using univariate Cox regression based on The Cancer Genome Atlas dataset. A predictive model related to stemness was constructed using Least Absolute Shrinkage and Selection Operator regression followed by multivariate Cox analysis.
RESULTS
Functional roles of NPC2 were validated using single-cell and bulk RNA sequencing data. Further experimental validation revealed that elevated NPC2 expression promoted tumor cell stemness, invasiveness, migratory ability, and resistance to standard chemotherapeutic agents. Importantly, high NPC2 expression correlated with poorer overall survival in GC patients.
CONCLUSION
In summary, the proposed model offers prognostic insights that outperform traditional clinical staging and may inform more tailored therapeutic approaches for gastric cancer management.
Core Tip: The results of this study indicate that the proposed gastric cancer (GC) stemness sensitivity model offers prognostic value that exceeds that of conventional clinicopathological staging, therefore providing more precise guidance for clinical decision-making and post-treatment management. The strong positive association between Niemann-Pick type C2 (NPC2) expression and GC progression highlights NPC2 as a promising prognostic biomarker. However, the functional role of NPC2 in GC remains insufficiently characterized. In this study, cellular experiments demonstrated that elevated expression of NPC2 enhances tumor cell stemness, invasiveness, migratory capacity, and resistance to radiotherapy and standard chemotherapeutic agents.
