Impact of genetic alterations on outcomes of patients with stage I nonsmall cell lung cancer: An analysis of the cancer genome atlas data.

Abstract

BackgroundThe prognostic factors for early‐stage nonsmall cell lung cancers (NSCLCs) are not well defined. This study aimed to investigate the effect of highly frequent mutations on the outcomes patients with early‐stage NSCLC, particularly those with surgically resected stage I disease.MethodsThe Cancer Genome Atlas (TCGA) datasets for Lung Adenocarcinoma (LUAD), Lung Squamous Cell Carcinoma (LUSC), and Pan‐Lung Cancer (PLC) were accessed via cBioportal and searched to identify patients with stage I NSCLC. We identified candidate genes with a high (>10%) frequency of mutations and copy‐number alterations and examined their effect on overall survival (OS) and disease‐free survival (DFS). The details of clinicopathologic features were analyzed with the Fisher's exact， Mann‐Whitney U test and Cox regression analysis. Survival was analyzed with Kaplan‐Meier curves, and differences were compared with the log‐rank and chi‐square test.ResultsWe identified 408 patients with stage I NSCLC from the PLC dataset. Of the 41 candidate genes with high‐frequency mutation rates, six genes were significantly associated with OS: TP53, LPP, MAP3K13, FGF12, BCL6, and TP63. Further stratified analysis in PLC, LUAD, and LUSC datasets, we only identified that TP53 was significantly associated with OS in patients with surgically resected stage I lung adenocarcinoma.Conclusions TP53 mutations are potentially markers of poor prognosis for stage I lung adenocarcinoma patients. The mutation status of this gene may contribute to clinical decision‐making with respect to selecting patients who may benefit from adjuvant therapy.