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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Feb 15, 2022; 14(2): 478-497
Published online Feb 15, 2022. doi: 10.4251/wjgo.v14.i2.478
Comprehensive molecular characterization and identification of prognostic signature in stomach adenocarcinoma on the basis of energy-metabolism-related genes
Jin-Jia Chang, Xiao-Yu Wang, Wei Zhang, Cong Tan, Wei-Qi Sheng, Mi-Die Xu
Jin-Jia Chang, Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
Jin-Jia Chang, Wei Zhang, Cong Tan, Wei-Qi Sheng, Mi-Die Xu, Department of Medical Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Xiao-Yu Wang, Laboratory of Immunology and Virology, Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
Wei Zhang, Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
Cong Tan, Wei-Qi Sheng, Mi-Die Xu, Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
Cong Tan, Wei-Qi Sheng, Mi-Die Xu, Institute of Pathology, Fudan University, Shanghai 200032, China
Author contributions: Chang JJ, Wang XY, Zhang W, Tan C, Sheng WQ and Xu MD designed the research; Chang JJ, Wang XY, Zhang W and Tan C performed the research; Tan C and Xu MD contributed analytic tools; Chang JJ, Wang XY and Zhang W analyzed the data and contributed equally to this work; Sheng WQ and Xu MD wrote the paper and share the corresponding authorship of this study.
Supported by the National Natural Science Foundation of China, No. 81972249, No. 81802367, No. 81802361 and No. 82172702; the Shanghai Clinical Research Plan of SHDC, No. SHDC2020CR4068; the Shanghai Clinical Science and Technology Innovation Project of Municipal Hospital, No. SHDC12020102; the Shanghai Science and Technology Development Fund, No. 18ZR1408000, No. 21ZR1414900 and No. 19MC1911000; the Clinical Research Project of Shanghai Municipal Health Committee, No. 20194Y0348; and the Shanghai “Rising Stars of Medical Talents” Youth Development Program Youth Medical Talents – Specialist Program, No. SHWSRS(2020)_087.
Institutional review board statement: Not applicable.
Conflict-of-interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Wei-Qi Sheng, PhD, Chief Doctor, Director, Professor, Teacher, Department of Pathology, Fudan University Shanghai Cancer Center, No. 270 Dong’an Road, Shanghai 200032, China. shengweiqi2006@163.com
Received: August 5, 2021
Peer-review started: August 5, 2021
First decision: October 3, 2021
Revised: October 9, 2021
Accepted: January 6, 2022
Article in press: January 6, 2022
Published online: February 15, 2022
Processing time: 189 Days and 13.6 Hours
BACKGROUND
Stomach adenocarcinoma (STAD) is a leading cause of cancer deaths, but its molecular and prognostic characteristics has never been fully illustrated.
AIM
To describe a molecular evaluation of primary STAD and develop new therapies and identify promising prognostic signatures.
METHODS
We describe a comprehensive molecular evaluation of primary STAD based on comprehensive analysis of energy-metabolism-related gene (EMRG) expression profiles.
RESULTS
On the basis of 86 EMRGs that were significantly associated to patients’ progression-free survival (PFS), we propose a molecular classification dividing gastric cancer into two subtypes: Cluster 1, most of which are young patients and display more immune and stromal cell components in tumor microenvironment and lower tumor priority; and Cluster 2, which show early stages and better PFS. Moreover, we construct a 6-gene signature that can classify the prognostic risk of patients after a three-phase training test and validation process. Compared with patients with low-risk score, patients with high-risk score had shorter overall survival. Furthermore, calibration and DCA analysis plots indicate the excellent predictive performance of the 6-gene signature, and which present higher robustness and clinical usability compared with three previous reported prognostic gene signatures. According to gene set enrichment analysis, gene sets related to the high-risk group were participated in the ECM receptor interaction and hedgehog signaling pathway.
CONCLUSION
Identification of the EMRG-based molecular subtypes and prognostic gene model provides a roadmap for patient stratification and trials of targeted therapies.
Core Tip: On the basis of 86 energy-metabolism-related gene that were significantly associated to patients’ progression-free survival (PFS), we propose a molecular classification dividing stomach adenocarcinoma into two subtypes: Cluster 1, most of which are young patients and display more immune and stromal cell components in tumor microenvironment and lower tumor priority; and Cluster 2, which show early stages and better PFS. Moreover, by using a three-phase training, test and validation process, we construct a 6-gene signature that can classify the prognostic risk of patients, and which present higher robustness and clinical usability compared with three previous reported prognostic gene signatures.
