Aging
Navigate
Submit an Article
Research Paper|Volume 15, Issue 15|pp 7476—7495

SETBP1 mutation determines sensitivity to immune checkpoint inhibitors in melanoma and NSCLC

Fengxiao An1, Wenjing Zhang2, Yuxian Guo2, Fuyan Shi2, Yujia Kong2, Liguo Tang3, Caijing Han4, Qinghua Wang2
  • 1Department of Clinical Laboratory, Affiliated Hospital of Weifang Medical University, Weifang 261031, Shandong, China
  • 2Department of Health Statistics, Key Laboratory of Medicine and Health of Shandong Province, School of Public Health, Weifang Medical University, Weifang 261053, Shandong, China
  • 3Department of Orthopedics, Sunshine Union Hospital, Weifang 261061, Shandong, China
  • 4School of Public Health, Weifang Medical University, Weifang 261053, Shandong, China
Received: April 11, 2023Accepted: June 23, 2023Published: August 2, 2023
https://doi.org/10.18632/aging.204913

Copyright: © 2023 An et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

SET binding protein 1 (SETBP1) plays crucial roles in various biological processes; however, its involvement in cancer immune checkpoint inhibitor (ICI) treatments has never been studied. In this study, we collected a total of 631 melanoma and 109 non-small cell lung cancer (NSCLC) samples treated with ICI agents (i.e., anti-CTLA-4, anti-PD-1/PD-L1, or combination therapy). Additionally, we obtained their corresponding somatic mutational profiles. We observed that SETBP1 mutated (SETBP1-MUT) melanoma patients exhibited significantly prolonged ICI survival outcomes compared to wild-type patients (HR: 0.56, 95% CI: 0.38-0.81, P = 0.002). Consistently, an elevated ICI response rate was also noticed in the SETBP1-MUT group (42.9% vs. 29.1%, P = 0.016). The Association of SETBP1 mutations with favorable immunotherapeutic prognosis and response was further supported by an independent NSCLC cohort (both P < 0.05). Additional immunological analyses revealed that favorable immune infiltration, tumor immunogenicity, and immune response circuits were enriched in SETBP1-MUT patients. Overall, our findings suggest that SETBP1 mutations may serve as a new biomarker for stratifying beneficiaries of ICI treatments in melanoma and NSCLC, which provides possible evidence for tailoring clinical immunotherapeutic strategies.