208P - Identification of BCOR mutation as a novel predictor of immunotherapy efficacy in gastrointestinal tumors

Background

Immune checkpoint inhibitors (ICIs) have become an important therapeutic option for gastrointestinal cancer (GC). BCOR (BCL6 Corepressor) is an epigenetic regulator, whose mutation has been found to be associated with the development of various tumors, while evidence in GC remains limited.

Methods

We analyze genomic data from 236 GC patients receiving immunotherapy from Memorial Sloan Kettering Cancer Center (MSKCC) to assess the relationship between BCOR mutation status and efficacy of immunotherapy. The prognostic value and RNA mechanism exploration of BCOR mutations are explored in 914 GC samples from The Cancer Genome Atlas (TCGA) database. CIBERSORT is used to evaluate the infiltration status of 22 immune cell types in TCGA GC cohort. Survival is estimated by Kaplan-Meiercurves, with the P-values are determined by log-ranktest.

Results

The TMB levels of BCOR-mutant (Mut) patients are higher than BCOR-wildtype (WT) patients in both TCGA (Median: 24.25 [0.55 - 245.56] vs. 2.78 [0.05 - 1296.91], P < 0.001) and MSKCC (Median: 54.65 [2.95 - 203.64] vs. 6.14 [0.00 - 93.04], P < 0.001) cohort. BCOR-Mut patients receiving ICIs achieve prolonged OS than BCOR-WT patients (median OS: 14 months vs. not reach; HR 95% CI: 0.28 (0.09-0.90); P = 0.03); moreover, a multivariable analysis using Cox proportional-hazards regression demonstrated that BCOR-Mut was associated with better OS (HR = 0.29; 95% CI: 0.092-0.93; P = 0.036), after adjusting for age, gender, metastasis and treatment. In TCGA cohort, there is no significance in OS between BCOR-wildtype and BCOR-mutant patients (median OS: 55.4 vs 61.8 months, P = 0.94). Based on the analysis of immune cell infiltration status, the mechanism of the predictive value of BCOR mutation to ICIs efficacy may be related to the greater abundance of activated CD4 memory T cell, CD8 T cell, follicular helper T cell and Macropghages M1, and lower abundance of Monocytes and CD4 memory resting cells in BCOR-mutant tumors.

Conclusions

Survival analysis of MSKCC shows BCOR mutation is an independent predictor of ICIs treatment in GC, rather than a prognostic factor, and may be associated with better immune cell infiltration.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.