B Cell Receptor Signaling Pathway Mutation as Prognosis Predictor of Immune Checkpoint Inhibitor for Lung Adenocarcinoma

Purpose: The advent of immune checkpoint inhibitors (ICIs) has generated a revolutionary breakthrough in the therapeutic treatment of many solid tumors, including lung adenocarcinoma (LUAD). However, the response rate of ICI therapy in patients with LUAD is low, so a clinical challenge has arisen in effectively using biomarkers to screen patients who can benefit from ICIs therapy. Methods: In this study, we divided patients according to BCR signaling pathway gene non-synonymous mutant or not, and established univariate and multivariate Cox regression models based on a LUAD cohort treated with ICI (Miao-LUAD), and examined the relationship between the mutation status of the BCR signaling pathway and the prognosis of immunotherapy. Then, combining the data from The Cancer Genome Atlas (TCGA) LUAD cohort, the Rizvi-LUAD, the Samstein-LUAD and the Zhujiang Hospital of Southern Medical University LUAD (Local-LUAD) cohort, the mutation panorama, immunogenicity, tumor microenvironment (TME) and pathway enrichment analysis between the BCR signaling pathway mutant group (BCR signaling MUT) and the BCR signaling pathway wild group (BCR signaling WT) were comprehensively compared. Results: It was found that, compared with the BCR signaling WT, the BCR signaling MUT had a significantly improved progression-free survival (PFS) and overall survival (OS), higher immunogenicity and immunoreactivity, and a pathway activation environment that was not conducive to the growth of tumor cells. Conclusion: These results revealed that the mutation state of the BCR signaling pathway has potential as a biomarker to predict the efficacy of ICIs.