Impact of genetic alterations on outcomes of patients with stage I nonsmall cell lung cancer: An analysis of the cancer genome atlas data
Song Xu, Yanye Wang, Fan Ren, Xiongfei Li, Dian Ren, Ming Dong, Gang Chen, Zuoqing Song, Jun Chen
Abstract
BACKGROUND: The 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. METHODS: The 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. RESULTS: We 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.