EPHA5 mutation predicts the durable clinical benefit of immune checkpoint inhibitors in patients with lung adenocarcinoma

Weimei HuangJian Zhang


Background: Immune checkpoint inhibitor (ICI ) therapy has shown remarkable clinical benefit in lung adenocarcinoma (LUAD) patients. Genomic mutations may be applicable to predict the response to ICIs. Eph receptor A5 (EPHA5) is frequently mutated in breast cancer, lung cancer and other tumors; however, its association with outcome in patients who receive immunotherapy remains unknown. Methods: Somatic mutation data, gene expression data and clinicopathologic information were curated from patients with LUAD who were treated with ICI therapy (MSKCC ICI-treated cohort) and patients with LUAD who did not receive ICI therapy (TCGA-LUAD cohort). The CIBERSORT and gene set enrichment analysis (GSEA) algorithms were separately used to infer the relative abundance of leukocytes and significantly enriched pathways in the defined subgroups. Tumor mutation burden (TMB), tumor neoantigen load, the fraction of copy number variants (CNVs), the mutation frequency of DNA damage repair (DDR) genes, and the prognosis of patients were compared between the EPHA5-mutated subgroup and the EPHA5 wild - type subgroup. Whole-exome sequencing (WES) data and drug sensitivity data downloaded from the Genomics of Drug Sensitivity in Cancer (GDSC) database ...Continue Reading

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