Distinctive targetable genotypes of younger patients with lung adenocarcinoma: a cBioPortal for cancer genomics data base analysis

Cancer Biol Ther. 2020;21(1):26-33. doi: 10.1080/15384047.2019.1665392. Epub 2019 Oct 9.

Abstract

There is still limited comprehensive genotyping data about young patients with lung adenocarcinoma. Herein, next generation sequencing (NGS) data of lung adenocarcinoma patients was retrospectively analyzed to evaluate the relationship between young age at diagnosis and the comprehensive molecular characteristics. The cBioPortal for Cancer Genomics database was queried for cancer genomic studies of lung adenocarcinoma and a cohort of 773 patients with complete cancer genomics data was selected from 2 of 11 studies. The relationship between age at diagnosis and frequency of targetable genotypes was analyzed and verified in another cohort composed of 177 Chinese lung adenocarcinoma patients undergoing NGS assay. Of the 773 eligible lung adenocarcinoma patients, younger age was associated with an increased likelihood of a targetable genotype (P < .001). Specifically, a higher prevalence of EGFR mutations (P = .005), ALK arrangements, ROS1 arrangements (P = .035) and RET arrangements (P < .001) were identified in younger patients. The frequency of KRAS mutations (P < .001) was significantly associated with older age at diagnosis and a similar trend existed for MET (P = .057) but not BRAF-V600E (P = .686) and ERBB2 (P = .083). Additionally, an age at diagnosis of 45 years was found to be a feasible cutoff point to differentiate the younger from the older patients by comprehensive molecular characteristics. These results indicated that younger patients with lung adenocarcinoma were associated with an increased likelihood of harboring a targetable genotype. Distinctive molecular characteristics were identified in patients younger than 45 years with lung adenocarcinoma, which highlights the importance of the NGS assay and personalized therapy in this subpopulation.

Keywords: Lung adenocarcinoma; next generation sequencing; targetable genotypes; young patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Databases, Factual
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Genomics / methods*
  • Genotype
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Prognosis
  • Retrospective Studies

Substances

  • Biomarkers, Tumor

Grants and funding

This work was supported by Taishan Scholar Foundation of Shandong Province (No.tshw201502061 to Xiaochun Zhang), Qingdao People’s Livelihood Science and Technology Program (16-6-2-3-nsh to Xiaochun Zhang), Chinese Postdoctoral Science Foundation (2017M622143 to Helei Hou) and Qingdao Postdoctoral Application Research Funded Project (2016052 to Helei Hou).