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

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

• non-small-cell lung cancer
• immunotherapy
• tumor mutation burden
• microsatellite instability
• programmed cell death protein-1
• gene mutation