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

Cancer Med. 2020 Oct;9(20):7686-7694. doi: 10.1002/cam4.3403. Epub 2020 Aug 28.

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.

Keywords: database; early stage; genomics; lung cancer; surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Biomarkers, Tumor*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • DNA Mutational Analysis
  • Female
  • Gene Frequency
  • Genetic Variation*
  • Genomics / methods
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Staging
  • Prognosis
  • Survival Analysis
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Biomarkers, Tumor
  • TP53 protein, human
  • Tumor Suppressor Protein p53