APOBEC3B and CD274 as Combined Biomarkers for Predicting Response to Immunotherapy in Urothelial Carcinoma of the Bladder.

Abstract

Immunotherapy has become a promising form of treatment for cancers. There is a need to predict response to immunotherapy accurately. In the UCSC Xena, pan-cancer analysis revealed a positive relationship between APOBEC3B (A3B) and tumor mutational burden (R = 0.28, P < 0.001) and microsatellite instability (R = 0.12, P < 0.05). Naturally, the A3B high expression group had higher tumor mutational burden and microsatellite instability than the low expression group. The bladder cancer (BLCA) cohort in The Cancer Genome Atlas (TCGA) revealed tumor mutational signatures of A3B high and low expression groups. Compared to the low expression group, the high expression group had a higher number of SNPs and mutations. Subsequently, A3B was profiled for immune cell infiltration and immune checkpoints in bladder cancer. The results showed that A3B was positively correlated with most immune cells. Compared with the A3B low expression group, the A3B high expression group had higher expression of immune checkpoints. A3B was positively correlated with CD274 (R = 0.12, P = 0.016). This indicated that the high expression of A3B may have a better response to immunotherapy. Furthermore, data from the IMvigor210 immunotherapy clinical trial was used to confirm the findings of this study. The combined survival analysis of A3B and CD274 showed that the group of patients with high expression of CD274 and A3B was found to have a significantly higher survival rate than the rest of the patient group (P < 0.047). The results demonstrated that A3B has a significant role in immunotherapy. Moreover, the combined biomarkers of A3B and CD274 were more effective in predicting response to immunotherapy in bladder urothelial carcinoma. The findings of this study provide valuable insights for precision medicine.