Analysis of BAI3 as a potential biomarker for lung cancer immunotherapy.

Abstract

e20556 Background: Brain angiogenesis inhibitor protein 3 (BAI3/ADGRB) belongs to the family of adhesion G protein-coupled receptors (GPCRs). Recently, emerging evidence has shown that BAI3 plays a role in the sensitivity of biliary duct cancer to immunotherapy. Here we explored the relationship between BAI3 mutation and potential effect of immunotherapy for lung cancer based on multidimensional data. Methods: The whole exome sequencing (WES) data of immune checkpoint inhibitor (ICI) treated lung cancer patients (n=137) were derived from cBioPortal website ( https://www.cbioportal.org ) to analyze the association between BAI3 mutation and efficacy of ICIs therapy. The TCGA genomic and RNA data for 963 lung cancers were used to evaluate tumor mutational burden (TMB) differences and potential mechanism between BAI3 mutation group and wildtype group. Results: In immunotherapy cohort, 10.9% (15/137) patients harbored BAI3 mutation. BAI3 mutant lung cancers had higher TMB level than wildtype patients (P<0.001). Patients with BAI3 mutation were identified to be associated with prolonged progression-free survival (PFS) than wildtype group (HR=0.25, 95%CI: 0.09-0.69, P=0.0036). A multivariable analysis using Cox proportional-hazards regression demonstrated that BAI3 mutation was significantly associated with better PFS (HR=0.22; 95%CI: 0.078-0.62; P = 0.004), adjusting for histology type, PD-L1 expression, gender, smoke status and treatment regimen. In TCGA cohort, 13.1% (126/963) lung cancers had BAI3 mutation. BAI3 mutant patients also had higher TMB than wildtype group (P<0.001). RNA data revealed that enhanced anti-tumor immunity, characterized by a higher abundance of CD8 T cells, was observed in BAI3 mutant tumors (P=0.028). Conclusions: BAI3-mutated lung cancer patients have a higher TMB, longer PFS with immunotherapy and show higher abundance of CD8 T cells. These results indicates that BAI3 mutation may serve as a potential biomarker of ICI benefit in lung cancers. Moreover, further clinical insights and prospective validation studies are warranted.