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

Qiuan Yang; Rong Shen; Hanlin Xu; Xiaoliang Shi; Lili Xu; Lin Zhang; Xinglong Fan; Xiangfeng Jin

doi:10.21037/atm-21-289

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

Ann Transl Med. 2021 Mar;9(6):465. doi: 10.21037/atm-21-289.

Authors

Qiuan Yang¹, Rong Shen², Hanlin Xu³, Xiaoliang Shi⁴, Lili Xu⁴, Lin Zhang⁴, Xinglong Fan⁵, Xiangfeng Jin⁶

Affiliations

¹ Department of Radiation Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
² Department of Chemotherapy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
³ Thoracic Department, The Affiliated Hospital of Qingdao University, Qingdao, China.
⁴ OrigiMed, Shanghai, China.
⁵ Thoracic Department, Qilu Hospital of Shandong University (Qingdao), Qingdao, China.
⁶ Thoracic Surgery Department, The Affiliated Hospital of Qingdao University, Qingdao, China.

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.

Keywords: PBRM1 expression; PBRM1 mutations; immune infiltrates; immunotherapy; multiple cancer types.