Meng XY, Yang D, Zhang B, Zhang T, Zheng ZC, Zhao Y. Glycolysis-related five-gene signature correlates with prognosis and immune infiltration in gastric cancer. World J Gastrointest Oncol 2024; 16(7): 3097-3117 [DOI: 10.4251/wjgo.v16.i7.3097]
Corresponding Author of This Article
Yan Zhao, MD, Doctor, Department of Gastric Surgery, Cancer Hospital of China Medical University/Liaoning Cancer Hospital & Institute/The Liaoning Provincial Key Laboratory of Interdisciplinary Research on Gastrointestinal Tumor Combining Medicine with Engineering, No. 44 Xiaoheyan Road, Dadong District, Shenyang 110042, Liaoning Province, China. doctorzhaoyan@126.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Clinical and Translational Research
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, 2024; 16(7): 3097-3117 Published online Jul 15, 2024. doi: 10.4251/wjgo.v16.i7.3097
Glycolysis-related five-gene signature correlates with prognosis and immune infiltration in gastric cancer
Xiang-Yu Meng, Dong Yang, Bao Zhang, Tao Zhang, Zhi-Chao Zheng, Yan Zhao
Xiang-Yu Meng, Dong Yang, Bao Zhang, Tao Zhang, Zhi-Chao Zheng, Yan Zhao, Department of Gastric Surgery, Cancer Hospital of China Medical University/Liaoning Cancer Hospital & Institute/The Liaoning Provincial Key Laboratory of Interdisciplinary Research on Gastrointestinal Tumor Combining Medicine with Engineering, Shenyang 110042, Liaoning Province, China
Author contributions: Meng XY and Zhao Y contributed to the study design; Meng XY, Yang D, and Zhang B participated in the data analysis, algorithms, and statistical analysis; Zhang T and Zhao Y were involved in the quality control of data and algorithms, and financial support; Meng XY prepared the manuscript; and all authors contributed to the manuscript editing and review.
Supported byTraining Program of the National Natural Science Foundation of China, No. 2021-ZLLH-05; National Cancer Center Climbing Fund, No. NCC201906B02; Shenyang Municipal Science and Technology Public Health Research and Development Special Project, No. 21-172-9-03 and No. 22-321-33-53; and Dalian University of Technology-Liaoning Cancer Hospital Medical Engineering Cross-Union Fund, No. LD202309.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Yan Zhao, MD, Doctor, Department of Gastric Surgery, Cancer Hospital of China Medical University/Liaoning Cancer Hospital & Institute/The Liaoning Provincial Key Laboratory of Interdisciplinary Research on Gastrointestinal Tumor Combining Medicine with Engineering, No. 44 Xiaoheyan Road, Dadong District, Shenyang 110042, Liaoning Province, China. doctorzhaoyan@126.com
Received: April 9, 2024 Revised: May 14, 2024 Accepted: June 13, 2024 Published online: July 15, 2024 Processing time: 94 Days and 7.1 Hours
Abstract
BACKGROUND
Gastric cancer (GC) is one of the most common malignancies worldwide. Glycolysis has been demonstrated to be pivotal for the carcinogenesis of GC.
AIM
To develop a glycolysis-based gene signature for prognostic evaluation in GC patients.
METHODS
Differentially expressed genes correlated with glycolysis were identified in stomach adenocarcinoma data (STAD). A risk score was established through a univariate Cox and least absolute shrinkage and selection operator analysis. The model was evaluated using the area under the receiver operating characteristic curves. RNA-sequencing data from high- and low-glycolysis groups of STAD patients were analyzed using Cibersort algorithm and Spearman correlation to analyze the interaction of immune cell infiltration and glycolysis. Multiomics characteristics in different glycolysis status were also analyzed.
RESULTS
A five-gene signature comprising syndecan 2, versican, malic enzyme 1, pyruvate carboxylase and SRY-box transcription factor 9 was constructed. Patients were separated to high- or low-glycolysis groups according to risk scores. Overall survival of patients with high glycolysis was poorer. The sensitivity and specificity of the model in prediction of survival of GC patients were also observed by receiver operating characteristic curves. A nomogram including clinicopathological characteristics and the risk score also showed good prediction for 3- and 5-year overall survival. Gene set variation analysis showed that high-glycolysis patients were related to dysregulation of pancreas beta cells and estrogen late pathways, and low-glycolysis patients were related to Myc targets, oxidative phosphorylation, mechanistic target of rapamycin complex 1 signaling and G2M checkpoint pathways. Tumor-infiltrating immune cells and multiomics analysis suggested that the different glycolysis status was significantly correlated with multiple immune cell infiltration. The patients with high glycolysis had lower tumor mutational burden and neoantigen load, higher incidence of microsatellite instability and lower chemosensitivity. High glycolysis status was often found among patients with grade 2/3 cancer or poor prognosis.
CONCLUSION
The genetic characteristics revealed by glycolysis could predict the prognosis of GC. High glycolysis significantly affects GC phenotype, but the detailed mechanism needs to be further studied.
Core Tip: A five-gene signature consisting of syndecan 2, versican, malic enzyme 1, pyruvate carboxylase, and SRY-box transcription factor 9 was constructed. Based on their risk scores, the patients were stratified into high- or low-glycolysis groups. The patients with high glycolysis were significantly poorer. The high-glycolysis patients revealed dysregulation of pancreas beta cells and estrogen late pathways, while low-glycolysis patients showed associations with Myc targets, oxidative phosphorylation, mechanistic target of rapamycin complex 1 signaling, and G2M checkpoint pathways. A significant correlation between different glycolysis statuses and multiple immune cell infiltrations was observed. The high glycolysis status was associated with lower tumor mutational burden, higher incidence of microsatellite instability-high, as well as reduced chemosensitivity among gastric cancer patients.
