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

doi:10.12998/wjcc.v10.i22.7772

Prognostic role of multiple abnormal genes in non-small-cell lung cancer

World J Clin Cases. 2022 Aug 6;10(22):7772-7784. doi: 10.12998/wjcc.v10.i22.7772.

Authors

Lu-Da Yan¹, Liu Yang¹, Na Li¹, Meng Wang¹, Yan-Hua Zhang¹, Wen Zhou¹, Zhi-Qiong Yu¹, Xiao-Chun Peng², Jun Cai³

Affiliations

¹ Department of Oncology, The First Affiliated Hospital of Yangtze University, Jingzhou 434023, Hubei Province, China.
² Department of Pathophysiology, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou 434023, Hubei Province, China.
³ Department of Oncology, The First Affiliated Hospital of Yangtze University, Jingzhou 434023, Hubei Province, China. 529369023@qq.com.

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