Research Paper Volume 14, Issue 18 pp 7547—7567
Pyroptosis patterns of colon cancer could aid to estimate prognosis, microenvironment and immunotherapy: evidence from multi-omics analysis
- 1 Department of Oncology, Shanxi Province Academy of Traditional Chinese Medicine, Shanxi Province Hospital of Traditional Chinese Medicine, Taiyuan, Shanxi 030012, China
- 2 Shanxi Clinical Research Center of Traditional Chinese Medicine Affiliated Shanxi Hospital of TCM, Taiyuan, Shanxi 030012, China
- 3 Department of Anesthesiology, Shanxi Provincial People’s Hospital, Taiyuan, Shanxi 030000, China
- 4 Central Laboratory, Shanxi Province Academy of Traditional Chinese Medicine, Taiyuan, Shanxi 030012, China
- 5 Affiliated Cancer Hospital, Shanxi Medical University, Taiyuan, Shanxi 030013, China
Received: May 6, 2022 Accepted: September 5, 2022 Published: September 23, 2022
https://doi.org/10.18632/aging.204302How to Cite
Copyright: © 2022 Zhou 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
Pyroptosis plays a critical role in the occurrence and development of colon cancer (CC). However, the specific mechanisms of pyroptosis patterns on immune regulation and tumor microenvironment (TME) formation in CC remain unclear. Based on 30 pyroptosis-related genes (PRGs), we evaluated the pyroptosis patterns of 1689 CC samples from the Cancer Genome Atlas and the Gene Expression Omnibus databases. The signatures of pyroptosis patterns and PRGs were identified in CC. In addition to systematically associating these patterns with TME cell infiltration characteristics, we constructed a pyroptosis signature score (PPSscore) to quantify pyroptosis patterns in individual tumor patients with immune responses. We discovered three distinct pyroptosis patterns, each with a different survival probability and being biologically relevant. TME infiltrating characteristics of revealed these patterns, consistent with immune-inflamed, immune-desert and immune-excluded phenotypes. Furthermore, a low PPSscore was associated with better clinical benefits. A high PPSscore was associated with a lower chance of survival due to its association with stromal activation. Additionally, two immunotherapy cohorts revealed that patients with lower PPSscore had better immune responses and durable clinical benefits. Our findings indicate that pyroptosis patterns play a vital role in immunoregulation and the formation of TME in CC.
Abbreviations
CC: colon cancer; TME: tumor microenvironment; PRGs: pyroptosis-related genes; PPSscore: pyroptosis signature score; OS: overall survival; ICIs: immune checkpoint inhibitors; TCGA: the Cancer Genome Atlas; GEO: Gene Expression Omnibus; CNV: copy number variations; DEGs: differentially expressed genes; GO: Gene Ontology; TMB: Tumor mutational burden; TCGA-COAD: the Cancer Genome Atlas-Colon Adenocarcinoma; GSVA: Gene Set Variation Analysis; ssGSEA: single-sample gene set enrichment analysis.