Comprehensive analyses of in multiple cancer types and its association with clinical response to immunotherapy and immune infiltrates.

BACKGROUND

The prognostic value of polybromo 1 () gene mutations in clear cell renal carcinoma (CCRCC) with anti-programmed death-ligand 1 (PD-L1) therapy remains controversial, and few studies have reported the impact of mutations in other cancer types.

METHODS

The patient information was obtained from cBioPortal and the Tumor Immune Estimation Resource (TIMER) databases. Mann-Whitney U test were used for correlation analysis. For survival analyses, Kaplan-Meier survival curves were used and compared using the log-rank test. Cox's regression model was used to perform univariable and multivariable analyses.

RESULTS

Our study, for the first time, performed comprehensive analyses of mutation frequency, expression, relationship of mutations with clinical benefit from immunotherapy, and expression with immune infiltrates in diverse cancer types. The results showed that the expression of was significantly lower in diverse cancer types compared with normal tissues. Based on multivariable analysis, mutations trended towards worse clinical outcomes from anti-PD-L1 in CCRCC, lung adenocarcinoma (LUAD), bladder urothelial carcinoma (BLCA), and skin cutaneous melanoma (SKCM), and a significant association was observed in LUAD and BLCA. mutations were associated with higher TMB in diverse cancer types and significant associations were observed in LUAD and BLCA. The expression of PBRM1 was found to positively correlate with immune infiltrates in diverse cancer types.

CONCLUSIONS

Our findings suggested caution in starting immunotherapy alone in mutant patients. Further studies are needed to improve treatment for mutant patients.