Author:
Cai Yonghua,Xiao Heng,Zhou Qixiong,Lin Jie,Liang Xianqiu,Xu Wei,Cao Yongfu,Zhang Xian,Wang Hai
Abstract
AbstractCell death resistance significantly contributes to poor therapeutic outcomes in various cancers. PANoptosis, a unique inflammatory programmed cell death (PCD) pathway activated by specific triggers and regulated by the PANoptosome, possesses key features of apoptosis, pyroptosis, and necroptosis, but these cannot be accounted for by any of the three PCD pathways alone. While existing studies on PANoptosis have predominantly centered on infectious and inflammatory diseases, its role in cancer malignancy has been understudied. In this comprehensive investigation, we conducted pan-cancer analyses of PANoptosome component genes across 33 cancer types. We characterized the genetic, epigenetic, and transcriptomic landscapes, and introduced a PANoptosome-related potential index (PANo-RPI) for evaluating the intrinsic PANoptosome assembly potential in cancers. Our findings unveil PANo-RPI as a prognostic factor in numerous cancers, including KIRC, LGG, and PAAD. Crucially, we established a significant correlation between PANo-RPI and tumor immune responses, as well as the infiltration of diverse lymphoid and myeloid cell subsets across nearly all cancer types. Moreover, a high PANo-RPI was consistently associated with improved immunotherapy response and efficacy, as evidenced by re-analysis of multiple immunotherapy cohorts. In conclusion, our study suggests that targeting PANoptosome components and modulating PANoptosis may hold tremendous therapeutic potential in the context of cancer.
Funder
Guangdong Basic and Applied Basic Research Foundation
Medical Scientific Research Foundation of Guangdong Province, China
General Guidance Project on Health Science and Technology in Guangzhou, Guangdong Province, China
Natural Science Foundation of Guangdong Province, China
President Foundation of Nanfang Hospital, Southern Medical University
Publisher
Springer Science and Business Media LLC