Comprehensive analyses of PBRM1 in multiple cancer types and its association with clinical response to immunotherapy and immune infiltrates

Abstract

Background: The prognostic value of polybromo 1 (PBRM1) 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 PBRM1 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 PBRM1 mutation frequency, PBRM1 expression, relationship of PBRM1 mutations with clinical benefit from immunotherapy, and PBRM1 expression with immune infiltrates in diverse cancer types. The results showed that the expression of PBRM1 was significantly lower in diverse cancer types compared with normal tissues. Based on multivariable analysis, PBRM1 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. PBRM1 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 PBRM1 mutant patients.Further studies are needed to improve treatment for PBRM1 mutant patients.

Mutational Analysis of PBRM1 and Significance of PBRM1 Mutation in Anti-PD-1 Immunotherapy of Clear Cell Renal Cell Carcinoma

“…However, mutations in PBRM1 have showed a negative impact on patient survival in ccRCC and BRCA (30)(31)(32).By comparing the effects of PBRM1 on OS and DFS in different tumors, we found that PBRM1 has significantly greater effects on ccRCC than in other tumors (Figure 3A). Some investigators have proposed PBRM1 as a target for therapy (33).…”

Ex vivo to in vivo model of malignant peripheral nerve sheath tumors for precision oncology

“…PBRM1 (polybromo1) is a DNA binding protein that is required for cell cycle progression through mitosis. PBRM1 mutant patients have been reported to respond poorly to immunotherapy (Yang et al , 2021). Copy number analysis also revealed significant genomic heterogeneity, with Chr8 aneuploidy being the most common event (10 of 13 pairs; Fig 1D ).…”

Linking Immunity with Genomics in Sarcomas: Is Genomic Complexity an Immunogenic Trigger?

“…For instance, mutations in PBRM1 associate with increased CTL infiltration and PD-L1 expression, as well as with decreased infiltration by regulatory T cells in clear cell renal cell carcinoma [84,85]. In addition, mutations in PBRM1 were also found predictive for worse clinical outcomes after PD-L1 blockade in various cancers, including clear cell renal cell carcinoma and lung adenocarcinoma, highlighting the ambiguous role of PBRM1 in immunity [86]. In chordomas, however, these findings suggest that alterations in the chromatin-remodeling complex, in part, could explain the extensive infiltration.…”