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Pyroptosis Patterns Characterized by Distinct Tumor Microenvironment Infiltration Landscapes in Gastric Cancer

Background: The potential role of pyroptosis in tumor microenvironment (TME) reprogramming and immunotherapy has received increasing attention. As most studies have concentrated on a single TME cell type or a single pyroptosis regulator (PR), the overall TME cell-infiltrating characteristics mediate...

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Autores principales: Xiang, Renshen, Ge, Yuhang, Song, Wei, Ren, Jun, Kong, Can, Fu, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535973/
https://www.ncbi.nlm.nih.gov/pubmed/34680930
http://dx.doi.org/10.3390/genes12101535
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author Xiang, Renshen
Ge, Yuhang
Song, Wei
Ren, Jun
Kong, Can
Fu, Tao
author_facet Xiang, Renshen
Ge, Yuhang
Song, Wei
Ren, Jun
Kong, Can
Fu, Tao
author_sort Xiang, Renshen
collection PubMed
description Background: The potential role of pyroptosis in tumor microenvironment (TME) reprogramming and immunotherapy has received increasing attention. As most studies have concentrated on a single TME cell type or a single pyroptosis regulator (PR), the overall TME cell-infiltrating characteristics mediated by the integrated roles of multiple PRs have not been comprehensively recognized. Methods: This study curated 33 PRs and conducted consensus clustering to identify distinct pyroptosis patterns in gastric cancer (GC) patients. A single-sample gene set enrichment analysis algorithm was used to quantify the infiltration density of TME immune cells and the enrichment scores of well-defined biological signatures. The pyroptosis patterns of individuals were quantified using a principal component analysis algorithm called the pyroptosis score (PS). Results: Three distinct pyroptosis patterns with significant survival differences were identified from 1422 GC samples; these patterns were closely associated with three TME cell-infiltrating landscapes—namely, the immune-inflamed, immune-excluded, and immune-desert phenotypes. The PS model generated on the basis of the pyroptosis pattern-related signature genes could accurately predict the TME status, existing molecular subtypes, genetic variation, therapeutic response, and clinical outcome; among which, a relatively high PS was highly consistent with immune activation, molecular subtypes with survival advantages, high tumor mutation burden, high microsatellite instability, and other favorable characteristics. In particular, from the Cancer Genome Atlas database, the PS model exhibited significant prognostic relevance in a pan-cancer analysis, and patients with a relatively high PS exhibited durable therapeutic advantages and better prognostic benefits in anti-PD1/L1 therapy. Conclusions: This study demonstrates that pyroptosis is prominently correlated with TME diversity and complexity, and quantification of the pyroptosis patterns of individuals will enhance our cognition of TME infiltration landscapes and help in formulating more effective immunotherapeutic strategies.
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spelling pubmed-85359732021-10-23 Pyroptosis Patterns Characterized by Distinct Tumor Microenvironment Infiltration Landscapes in Gastric Cancer Xiang, Renshen Ge, Yuhang Song, Wei Ren, Jun Kong, Can Fu, Tao Genes (Basel) Article Background: The potential role of pyroptosis in tumor microenvironment (TME) reprogramming and immunotherapy has received increasing attention. As most studies have concentrated on a single TME cell type or a single pyroptosis regulator (PR), the overall TME cell-infiltrating characteristics mediated by the integrated roles of multiple PRs have not been comprehensively recognized. Methods: This study curated 33 PRs and conducted consensus clustering to identify distinct pyroptosis patterns in gastric cancer (GC) patients. A single-sample gene set enrichment analysis algorithm was used to quantify the infiltration density of TME immune cells and the enrichment scores of well-defined biological signatures. The pyroptosis patterns of individuals were quantified using a principal component analysis algorithm called the pyroptosis score (PS). Results: Three distinct pyroptosis patterns with significant survival differences were identified from 1422 GC samples; these patterns were closely associated with three TME cell-infiltrating landscapes—namely, the immune-inflamed, immune-excluded, and immune-desert phenotypes. The PS model generated on the basis of the pyroptosis pattern-related signature genes could accurately predict the TME status, existing molecular subtypes, genetic variation, therapeutic response, and clinical outcome; among which, a relatively high PS was highly consistent with immune activation, molecular subtypes with survival advantages, high tumor mutation burden, high microsatellite instability, and other favorable characteristics. In particular, from the Cancer Genome Atlas database, the PS model exhibited significant prognostic relevance in a pan-cancer analysis, and patients with a relatively high PS exhibited durable therapeutic advantages and better prognostic benefits in anti-PD1/L1 therapy. Conclusions: This study demonstrates that pyroptosis is prominently correlated with TME diversity and complexity, and quantification of the pyroptosis patterns of individuals will enhance our cognition of TME infiltration landscapes and help in formulating more effective immunotherapeutic strategies. MDPI 2021-09-28 /pmc/articles/PMC8535973/ /pubmed/34680930 http://dx.doi.org/10.3390/genes12101535 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xiang, Renshen
Ge, Yuhang
Song, Wei
Ren, Jun
Kong, Can
Fu, Tao
Pyroptosis Patterns Characterized by Distinct Tumor Microenvironment Infiltration Landscapes in Gastric Cancer
title Pyroptosis Patterns Characterized by Distinct Tumor Microenvironment Infiltration Landscapes in Gastric Cancer
title_full Pyroptosis Patterns Characterized by Distinct Tumor Microenvironment Infiltration Landscapes in Gastric Cancer
title_fullStr Pyroptosis Patterns Characterized by Distinct Tumor Microenvironment Infiltration Landscapes in Gastric Cancer
title_full_unstemmed Pyroptosis Patterns Characterized by Distinct Tumor Microenvironment Infiltration Landscapes in Gastric Cancer
title_short Pyroptosis Patterns Characterized by Distinct Tumor Microenvironment Infiltration Landscapes in Gastric Cancer
title_sort pyroptosis patterns characterized by distinct tumor microenvironment infiltration landscapes in gastric cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535973/
https://www.ncbi.nlm.nih.gov/pubmed/34680930
http://dx.doi.org/10.3390/genes12101535
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