Related Experiment Video
Updated: Jul 1, 2025
Immunophenotyping of Orthotopic Homograft Syngeneic of Murine Primary KPC Pancreatic Ductal Adenocarcinoma by Flow Cytometry
Published on: October 9, 2018
Comprehensive Analyses of PANoptosome with Potential Implications in Cancer Prognosis and Immunotherapy
Yonghua Cai1, Heng Xiao2, Qixiong Zhou1
1Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China.
Abstract:
Cell 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.
Insights
PANoptosis, an inflammatory cell death pathway, is understudied in cancer. This research introduces a PANoptosome-related index (PANo-RPI) linking it to prognosis, immune response, and better immunotherapy outcomes in various cancers.
Area of Science:
- Oncology
- Immunology
- Cell Death Research
Background:
- Cell death resistance is a major challenge in cancer therapy.
- PANoptosis is a distinct inflammatory programmed cell death (PCD) pathway involving the PANoptosome, with features of apoptosis, pyroptosis, and necroptosis.
- The role of PANoptosis in cancer malignancy remains largely unexplored, with most research focused on infectious and inflammatory diseases.
Purpose of the Study:
- To conduct a comprehensive pan-cancer analysis of PANoptosome component genes.
- To characterize the genetic, epigenetic, and transcriptomic landscapes of PANoptosome components across 33 cancer types.
- To develop and validate a PANoptosome-related potential index (PANo-RPI) for assessing intrinsic PANoptosome assembly potential and its prognostic and immunotherapeutic implications in cancer.
Main Methods:
- Pan-cancer analysis of PANoptosome component genes across 33 cancer types.
- Characterization of genetic, epigenetic, and transcriptomic landscapes.
- Development of a PANoptosome-related potential index (PANo-RPI).
- Correlation analysis with tumor immune responses, immune cell infiltration, and immunotherapy efficacy.
Main Results:
- The PANo-RPI was identified as a prognostic factor in several cancers (e.g., KIRC, LGG, PAAD).
- PANo-RPI significantly correlates with tumor immune responses and the infiltration of lymphoid and myeloid cells across most cancer types.
- Higher PANo-RPI is consistently associated with improved responses to immunotherapy.
Conclusions:
- PANoptosis and its regulator, the PANoptosome, play a significant role in cancer malignancy.
- The PANo-RPI serves as a valuable biomarker for predicting prognosis and immunotherapy response.
- Targeting PANoptosome components and modulating PANoptosis presents a promising therapeutic strategy for cancer treatment.
