Massive Digital Gene Expression Analysis Reveals Different Predictive Profiles for Immune Checkpoint Inhibitor Therapy Between Adenocarcinoma and Squamous Cell Carcinoma of Advanced Lung Cancer

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 an exhaustive 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-DPB1and CDH2genes was observed in responders with squamous cell carcinoma.Conclusions: This study predicted the efficacy of nivolumab based on an exhaustive analysis of mRNA expression at the gene level in advanced NSCLC. We also revealed different gene expression patterns as predictors of the effectiveness ofanti PD-1 antibody therapy in adenocarcinoma and squamous cell carcinoma.