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©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
Identification of a three-gene prognostic signature for radioresistant esophageal squamous cell carcinoma
Xiao-Yan Wang, Narasimha M Beeraka, Nan-Nan Xue, Hui-Ming Yu, Ya Yang, Mao-Xing Liu, Vladimir N Nikolenko, Jun-Qi Liu, Di Zhao
Xiao-Yan Wang, Di Zhao, Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Narasimha M Beeraka, Nan-Nan Xue, Ya Yang, Jun-Qi Liu, Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Narasimha M Beeraka, Vladimir N Nikolenko, Department of Human Anatomy, I. M. Sechenov First Moscow State Medical University, Moscow 119991, Russia
Narasimha M Beeraka, Department of Pharmaceutical Chemistry, JSS College of Pharmacy, Mysuru 570015, India
Hui-Ming Yu, Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 065005, China
Mao-Xing Liu, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing, China
Vladimir N Nikolenko, M.V. Lomonosov Moscow State University, Moscow 119991, Russia
Author contributions: Wang XY, Beeraka NM, Xue NN, Yu HM, Yang Y, Liu MX, Nikolenko VN, Liu JQ, and Zhao D conceptualized and designed the study; Beeraka NM, Wang XY, Liu JQ, Zhao D, Xue NN, Yu HM, Nikolenko VN, and Yang Y performed the literature analysis and drafted the manuscript; Beeraka NM, Liu JQ, and Zhao D revised, edited, and extended the final draft; all authors have reviewed and approved the manuscript before submission; Wang XY and Beeraka NM contributed equally to this work.
Institutional review board statement: Since the data of this study were obtained from the TCGA and GEO public databases, in which no personal identification information was included, informed consent was waived by the First Affiliated Hospital of Zhengzhou University.
Conflict-of-interest statement: All the authors declare that they have no conflict of interest to disclose.
Data sharing statement: All the supplementary files can be provided upon request by the editorial office as the data was obtained from the TCGA and GEO databases.
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 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:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Di Zhao, MD, Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshedong Street, Zhengzhou, 450052, Henan Province, China. zhaodi0110@126.com
Received: July 25, 2022
Peer-review started: July 25, 2022
First decision: October 24, 2022
Revised: October 25, 2022
Accepted: December 6, 2022
Article in press: December 6, 2022
Published online: January 24, 2023
ARTICLE HIGHLIGHTS
Research background
Esophageal squamous cell carcinoma (ESCC) is causing a high mortality rate due to the lack of efficient early prognosis markers and suitable therapeutic regimens.
Research motivation
The prognostic role of genes responsible for the acquisition of radioresistance in ESCC has not been fully elucidated.
Research objectives
To establish a prognostic model by studying gene expression patterns pertinent to radioresistance in ESCC patients.
Research methods
Datasets were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases. The edgeR, a Bioconductor package, was used to analyze mRNA expression between different groups. We screened genes specifically responsible for radioresistance to estimate overall survival. Pearson correlation analysis was performed to confirm whether the expression of those genes correlated with each other. Genes contributing to radioresistance and overall survival were assessed by the multivariate Cox regression model through the calculation of βi and risk score using the following formula: 
.
Research results
We identified three prognostic mRNAs (cathepsin S [CTSS], cluster of differentiation 180 [CD180], and SLP adapter and CSK-interacting membrane protein [SCIMP]) indicative of radioresistance. The expression of the three identified mRNAs was related to each other (r > 0.70 and P < 0.05). As to 1-year and 3-year overall survival prediction, the area under the time-dependent receiver operating characteristic curve of the signature consisting of the three mRNAs was 0.716 and 0.841, respectively. When stratifying patients based on the risk score derived from the signature, the high-risk group exhibited a higher death risk and shorter survival time than the low-risk group (P < 0.0001). Overall survival of the low-risk patients was significantly better than that of the high-risk patients (P = 0.018).
Research conclusions
We have developed a novel three-gene prognostic signature consisting of CTSS, CD180, and SCIMO for ESCC.
Research perspectives
The three-gene signature developed in this study may facilitate the prediction of early prognosis of this malignancy.
