Abstract 3320: A comprehensive pan-cancer analysis of BCOR as a promising biomarker for immune checkpoint inhibitor therapy

Abstract Background: BCOR is a gene that encodes an epigenetic regulator, which is indispensable for guiding cell differentiation and body structure development. While immune checkpoint inhibitors (ICIs) have emerged as a significant therapeutic option for tumor patients, the correction between BCOR mutations and the efficacy of ICIs in solid tumors remains uncertain. Methods: Next-generation sequencing (NGS) and clinical data of pan-cancer patients were sourced from two MSK-IMPACT cohorts: MSK-2017, comprising 10336 patients, and MSK-2019, consisting of 1661 patients. The MSK-2019 cohort treated with ICIs underwent analysis to investigate the correlation between BCOR mutations and the therapeutic efficacy of ICIs. mRNA expression data of 10228 pan-cancer patients were retrieved from the TCGA database, aiming to explore the relationship between BCOR expression levels and immune cell infiltration. Results: Totally, 2.9% (304/10336) of pan-cancer patients in the MSK-2017 cohort and 3.9% (64/1661) in the MSK-2019 cohort harbored BCOR mutations. In the MSK-2017 cohort, the top three tumor types with the highest frequency of BCOR mutations were endometrial cancer (28/218, 12.8%), adrenocortical carcinoma (3/25, 12.0%), and salivary gland cancer (9/114, 7.9%), respectively. Differently, the MSK-2019 cohort showed the highest frequency of BCOR mutations in colorectal cancer (11/110, 10.0%), whereas in the MSK-2017 cohort, BCOR mutations were only observed in 3.5% (35/1007) of colorectal cancer patients. The most common types of BCOR mutations in both cohorts were missense and truncating mutations. In the MSK-2019 cohort, the BCOR-mutated group exhibited a significantly higher tumor mutational burden (TMB) compared to the BCOR-wild group (median TMB: mutated-type vs. wild-type = 36.7 vs. 5.9 Muts/Mb, P<0.0001). Additionally, the overall survival (OS) of the BCOR-mutated group was significantly longer than that of the wild-type group (median OS: 36.0 vs. 15.0 months; hazard ratio [HR]=0.5, 95% confidence interval [CI]: 0.6-0.7, P=0.003). However, in MSK-2017 cohort treated without immunotherapy, there was no difference in OS between BCOR-mutated group and BCOR-wild group (median OS, 30.0 vs. 26.0 months; HR=0.9, 95%CI: 0.7-1.1, P=0.3). The immuno-correlation analysis showed that across most tumor types, the infiltration levels of CD4+ memory resting T cell, plasma B cell, and naive B cell exhibited a positive correlation with BCOR expression. Conversely, the infiltration levels of regulatory T cells, gamma delta T cells, and follicular helper T cells exhibited a negative correlation with BCOR expression. Conclusion: The results indicated that the BCOR mutation frequency varied across different tumor types and cohorts. Notably, in patients treated with ICIs, BCOR mutations were associated with higher TMB and improved OS, suggesting its potential as a biomarker in immunotherapy response. Citation Format: Cairui Li, Shuguang Sun, Kaiye Dong, Yaping Zhu, Xuefeng Zhong. A comprehensive pan-cancer analysis of BCOR as a promising biomarker for immune checkpoint inhibitor therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3320.