Retrospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Sep 16, 2022; 10(26): 9285-9302
Published online Sep 16, 2022. doi: 10.12998/wjcc.v10.i26.9285
Development and validation of an epithelial–mesenchymal transition-related gene signature for predicting prognosis
De-Hua Zhou, Qian-Cheng Du, Zheng Fu, Xin-Yu Wang, Ling Zhou, Jian Wang, Cheng-Kai Hu, Shun Liu, Jun-Min Li, Meng-Li Ma, Hua Yu
De-Hua Zhou, Xin-Yu Wang, Ling Zhou, Hua Yu, Department of General Surgery, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai 200434, China
Qian-Cheng Du, Zheng Fu, Jian Wang, Cheng-Kai Hu, Shun Liu, Department of Thoracic surgery, Shanghai Xuhui Central Hospital, Shanghai 200031, China
Jun-Min Li, Meng-Li Ma, Surgical Intensive Care Unit, Shanghai Xuhui Central Hospital, Shanghai 200031, China
Author contributions: Zhou DH and Du QC analyzed the data and wrote the manuscript, and both contributed equally to this work; Yu H designed the study; Wang XY, Fu Z, Zhou L, Wang J, Hu CK, Liu S, Li JM and Ma ML collected the data and revised the paper. All authors have read and approved the final manuscript.
Institutional review board statement: The data for the study came from public databases and did not involve blood or tissue samples from humans or animals. Therefore, there were no ethical issues involved in this study.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: No additional data are available.
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: Hua Yu, MM, Associate Chief Physician, Department of General Surgery, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, No. 1279 Sanmen Road, Shanghai 200434, China. luckyyuhua@163.com
Received: April 2, 2022
Peer-review started: April 2, 2022
First decision: June 16, 2022
Revised: June 30, 2022
Accepted: July 20, 2022
Article in press: July 20, 2022
Published online: September 16, 2022
Processing time: 152 Days and 14.5 Hours
Abstract
BACKGROUND

Currently, there are many therapeutic methods for lung adenocarcinoma (LUAD), but the 5-year survival rate is still only 15% at later stages. Epithelial– mesenchymal transition (EMT) has been shown to be closely associated with local dissemination and subsequent metastasis of solid tumors. However, the role of EMT in the occurrence and development of LUAD remains unclear.

AIM

To further elucidate the value of EMT-related genes in LUAD prognosis.

METHODS

Univariate, least absolute shrinkage and selection operator, and multivariate Cox regression analyses were applied to establish and validate a new EMT-related gene signature for predicting LUAD prognosis. The risk model was evaluated by Kaplan–Meier survival analysis, principal component analysis, and functional enrichment analysis and was used for nomogram construction. The potential structures of drugs to which LUAD is sensitive were discussed with respect to EMT-related genes in this model.

RESULTS

Thirty-three differentially expressed genes related to EMT were found to be highly associated with overall survival (OS) by using univariate Cox regression analysis (log2FC ≥ 1, false discovery rate < 0.001). A prognostic signature of 7 EMT-associated genes was developed to divide patients into two risk groups by high or low risk scores. Kaplan–Meier survival analysis showed that the OS of patients in the high-risk group was significantly poorer than that of patients in the low-risk group (P < 0.05). Multivariate Cox regression analysis showed that the risk score was an independent risk factor for OS (HR > 1, P < 0.05). The results of receiver operator characteristic curve analysis suggested that the 7-gene signature had a perfect ability to predict prognosis (all area under the curves > 0.5).

CONCLUSION

The EMT-associated gene signature classifier could be used as a feasible indicator for predicting OS.

Keywords: Lung adenocarcinoma; Epithelial–mesenchymal transition; Gene signature; Overall survival

Core Tip: Lung cancer is one of the major causes of death associated with malignancy, and lung cancer is associated with approximately 2 million new cases and 1.76 million deaths every year. Although some reports have shown that suppression or knockdown of some genes in lung adenocarcinoma (LUAD) could reverse the epithelial–mesenchymal transition (EMT) process that inhibits tumor occurrence and metastasis, the correlations of these genes with overall survival in patients with LUAD remain largely unclear. A cohort of 884 LUAD patients was used to construct and validate a novel predictive model comprising a 7-EMT-related gene signature, which can be used to predict the prognosis of LUAD.