Retrospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Aug 6, 2022; 10(22): 7772-7784
Published online Aug 6, 2022. doi: 10.12998/wjcc.v10.i22.7772
Prognostic role of multiple abnormal genes in non-small-cell lung cancer
Lu-Da Yan, Liu Yang, Na Li, Meng Wang, Yan-Hua Zhang, Wen Zhou, Zhi-Qiong Yu, Xiao-Chun Peng, Jun Cai
Lu-Da Yan, Liu Yang, Na Li, Meng Wang, Yan-Hua Zhang, Wen Zhou, Zhi-Qiong Yu, Jun Cai, Department of Oncology, The First Affiliated Hospital of Yangtze University, Jingzhou 434023, Hubei Province, China
Xiao-Chun Peng, Department of Pathophysiology, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, Hubei Province, China
Author contributions: Yan LD, Peng XC, and Cai J designed the research; Yan LD, Yang L, Na Li, Peng XC, and Cai J performed the research; Wang M, Zhang YH, Zhou W, and Yu ZQ contributed new reagents/analytic tools; Yan LD, Peng XC, and Cai J analyzed the data; Yan LD and Cai J wrote the paper.
Supported by the Natural Science Foundation of Hubei Province, No. 2017CFB786; the Hubei Province Health and Family Planning Scientific Research Project, No. WJ2016Y10; the Jingzhou Science and Technology Bureau Project, No. 2017-93; and the College Students Innovative Entrepreneurial Training Program in Yangtze University, No. 2019376.
Institutional review board statement: The study was reviewed and approved by the Health Science Center of Yangtze University Institutional Review Board (Approval No. 2020-036).
Informed consent statement: The requirement to obtain informed consent was waived by Yangtze University Ethics Board.
Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose.
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: Jun Cai, MD, PhD, Chief Doctor, Department of Oncology, The First Affiliated Hospital of Yangtze University, No. 1 Nanhuan Road, Jingzhou 434023, Hubei Province, China. 529369023@qq.com
Received: February 28, 2022
Peer-review started: February 28, 2022
First decision: May 11, 2022
Revised: May 19, 2022
Accepted: June 17, 2022
Article in press: June 17, 2022
Published online: August 6, 2022
Processing time: 143 Days and 23.2 Hours
Abstract
BACKGROUND

Non-small-cell lung cancer (NSCLC) has the highest morbidity and mortality rates among all malignant tumor types. Although therapies targeting the mutated genes such as KRAS have been used in the clinic for many years, the prognosis remains poor. Therefore, it is necessary to further study the aberrant expression or mutation of non-target genes affecting the survival and prognosis.

AIM

To explore the impact of simultaneous abnormalities of multiple genes on the prognosis and survival of patients.

METHODS

We used R packages to analyze gene expression data and clinical data downloaded from The Cancer Genome Atlas (TCGA) database. We also collected samples from 85 NSCLC patients from the First People’s Hospital of Jingzhou City and retrospectively followed the patients. Multivariate Cox regression analysis and survival analysis were performed.

RESULTS

Analysis of gene expression data from TCGA revealed that the overexpression of the following single genes affected overall survival: TP53 (P = 0.79), PTEN (P = 0.94), RB1 (P = 0.49), CTNNB1 (P = 0.24), STK11 (P = 0.32), and PIK3CA (P = 0.013). However, the probability of multiple genes (TP53, PTEN, RB1, and STK11) affecting survival was 0.025. Retrospective analysis of clinical data revealed that sex (hazard ratio [HR] = 1.29; [95%CI: 0.64-2.62]), age (HR = 1.05; [95%CI: 1.02-1.07]), smoking status (HR = 2.26; [95%CI: 1.16-4.39]), tumor histology (HR = 0.58; [95%CI: 0.30-1.11]), cancer stage (HR = 16.63; [95%CI: 4.8-57.63]), epidermal growth factor receptor (EGFR) mutation (HR = 1.82; [95%CI: 1.05-3.16]), abundance (HR = 4.95; [95%CI: 0.78-31.36]), and treatment with tyrosine kinase inhibitors (TKIs) (HR = 0.58; [95%CI: 0.43-0.78]) affected patient survival. Co-occurring mutations of TP53, PTEN, RB1, and STK11 did not significantly affect the overall survival of patients receiving chemotherapy (P = 0.96) but significantly affected the overall survival of patients receiving TKIs (P = 0.045).

CONCLUSION

Co-occurring mutation or overexpression of different genes has different effects on the overall survival and prognosis of NSCLC patients. Combined with TKI treatment, the co-occurring mutation of some genes may have a synergistic effect on the survival and prognosis of NSCLC patients.

Keywords: Non-small-cell lung cancer; Gene mutation; Tyrosine kinase inhibitor; Overexpression; Next-generation sequencing; Epidermal growth factor receptor; KRAS

Core Tip: Non-small-cell lung cancer (NSCLC) has the highest morbidity and mortality rates among all malignant tumors. To explore the impact of simultaneous abnormalities of multiple genes on the prognosis and survival of patients. We used R packages to analyze gene expression data and clinical data downloaded from The Cancer Genome Atlas database. We also collected samples from 85 NSCLC patients from the First People's Hospital of Jingzhou City and retrospectively followed the patients for multivariate Cox regression analysis and survival analysis. Co-occurring mutation or overexpression of different genes has different effects on the overall survival and prognosis of patients. Combined with TKI treatment, the co-occurring mutation of some genes may have a synergistic effect on the survival and prognosis of NSCLC patients.