Massive digital gene expression analysis reveals different predictive profiles for immune checkpoint inhibitor therapy between adenocarcinoma and squamous cell carcinoma of advanced lung cancer

BMC Cancer. 2022 Feb 8;22(1):154. doi: 10.1186/s12885-022-09264-2.

Abstract

Background: Immune checkpoint inhibitors prolong the survival of non-small cell lung cancer (NSCLC) patients. Although it has been acknowledged that there is some correlation between the efficacy of anti-programmed cell death-1 (PD-1) antibody therapy and immunohistochemical analysis, this technique is not yet considered foolproof for predicting a favorable outcome of PD-1 antibody therapy. We aimed to predict the efficacy of nivolumab based on a comprehensive analysis of RNA expression at the gene level in advanced NSCLC.

Methods: This was a retrospective study on patients with NSCLC who were administered nivolumab at the Kansai Medical University Hospital. To identify genes associated with response to anti-PD-1 antibodies, we grouped patients into responders (complete and partial response) and non-responders (stable and progressive disease) to nivolumab therapy. Significant genes were then identified for these groups using Welch's t-test.

Results: Among 42 analyzed cases (20 adenocarcinomas and 22 squamous cell carcinomas), enhanced expression of MAGE-A4, BBC3, and OTOA genes was observed in responders with adenocarcinoma, and enhanced expression of DAB2, HLA-DPB,1 and CDH2 genes was observed in responders with squamous cell carcinoma.

Conclusions: This study predicted the efficacy of nivolumab based on a comprehensive analysis of mRNA expression at the gene level in advanced NSCLC. We also revealed different gene expression patterns as predictors of the effectiveness of anti PD-1 antibody therapy in adenocarcinoma and squamous cell carcinoma.

Keywords: Advanced non-small cell lung cancer; Anti PD-1 antibody; Nivolumab; Transcriptome.

MeSH terms

  • Adaptor Proteins, Signal Transducing / immunology
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / immunology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / immunology
  • Antigens, Neoplasm / immunology
  • Apoptosis Regulatory Proteins / immunology
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / immunology
  • Cadherins / immunology
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / immunology
  • Drug Resistance, Neoplasm / genetics
  • Drug Resistance, Neoplasm / immunology
  • Female
  • GPI-Linked Proteins / immunology
  • Gene Expression / drug effects
  • Gene Expression / immunology
  • HLA-DP beta-Chains / immunology
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology
  • Male
  • Middle Aged
  • Neoplasm Proteins / immunology
  • Nivolumab / therapeutic use*
  • Predictive Value of Tests
  • Programmed Cell Death 1 Receptor / drug effects
  • Programmed Cell Death 1 Receptor / immunology
  • Proto-Oncogene Proteins / immunology
  • RNA, Messenger / drug effects
  • RNA, Messenger / immunology
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • Antigens, Neoplasm
  • Apoptosis Regulatory Proteins
  • BBC3 protein, human
  • Biomarkers, Tumor
  • CDH2 protein, human
  • Cadherins
  • DAB2 protein, human
  • GPI-Linked Proteins
  • HLA-DP beta-Chains
  • HLA-DPB1 antigen
  • Immune Checkpoint Inhibitors
  • MAGEA4 protein, human
  • Neoplasm Proteins
  • OTOA protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Nivolumab