Detection of Potential Mutated Genes Associated with Common Immunotherapy Biomarkers in Non-Small-Cell Lung Cancer Patients

Curr Oncol. 2022 Aug 15;29(8):5715-5730. doi: 10.3390/curroncol29080451.

Abstract

Microsatellite instability (MSI), high tumor mutation burden (TMB-H) and programmed cell death 1 ligand 1 (PD-L1) expression are hot biomarkers related to the improvement of immunotherapy response. Two cohorts of non-small-cell lung cancer (NSCLC) were collected and sequenced via targeted next-generation sequencing. Drug analysis was then performed on the shared genes using three different databases: Drugbank, DEPO and DRUGSURV. A total of 27 common genes were mutated in at least two groups of TMB-H-, MSI- and PD-L1-positive groups. AKT1, SMAD4, SCRIB and AXIN2 were severally involved in PI3K-activated, transforming growth factor beta (TGF-β)-activated, Hippo-repressed and Wnt-repressed pathways. This study provides an understanding of the mutated genes related to the immunotherapy biomarkers of NSCLC.

Keywords: gene mutation; immunotherapy; microsatellite instability; non-small-cell lung cancer; programmed cell death protein-1; tumor mutation burden.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Humans
  • Immunotherapy
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Microsatellite Instability
  • Mutation

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor

Grants and funding

This work was supported by the Chinese Academy of Medical Sciences’ Medical and Health Science of Technology Innovation Project “Systematic biomedical studies on inflammatory lung injury and repair” under grant number 2017-I2M-1-009.