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The Pyroptosis-Related Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Gastric Cancer

Gastric cancer (GC) is one of the leading causes of cancer-related deaths and shows high levels of heterogeneity. The development of a specific prognostic model is important if we are to improve treatment strategies. Pyroptosis can arise in response to H. pylori, a primary carcinogen, and also in re...

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Autores principales: Shao, Wei, Yang, Zongcheng, Fu, Yue, Zheng, Lixin, Liu, Fen, Chai, Li, Jia, Jihui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226259/
https://www.ncbi.nlm.nih.gov/pubmed/34179006
http://dx.doi.org/10.3389/fcell.2021.676485
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author Shao, Wei
Yang, Zongcheng
Fu, Yue
Zheng, Lixin
Liu, Fen
Chai, Li
Jia, Jihui
author_facet Shao, Wei
Yang, Zongcheng
Fu, Yue
Zheng, Lixin
Liu, Fen
Chai, Li
Jia, Jihui
author_sort Shao, Wei
collection PubMed
description Gastric cancer (GC) is one of the leading causes of cancer-related deaths and shows high levels of heterogeneity. The development of a specific prognostic model is important if we are to improve treatment strategies. Pyroptosis can arise in response to H. pylori, a primary carcinogen, and also in response to chemotherapy drugs. However, the prognostic evaluation of GC to pyroptosis is insufficient. Consensus clustering by pyroptosis-related regulators was used to classify 618 patients with GC from four GEO cohorts. Following Cox regression with differentially expressed genes, our prognosis model (PS-score) was built by LASSO-Cox analysis. The TCGA-STAD cohort was used as the validation set. ESTIMATE, CIBERSORTx, and EPIC were used to investigate the tumor microenvironment (TME). Immunotherapy cohorts by blocking PD1/PD-L1 were used to investigate the treatment response. The subtyping of GC based on pyroptosis-related regulators was able to classify patients according to different clinical traits and TME. The difference between the two subtypes identified in this study was used to develop a prognosis model which we named “PS-score.” The PS-score could predict the prognosis of patients with GC and his/her overall survival time. A low PS-score implies greater inflammatory cell infiltration and better response of immunotherapy by PD1/PD-L1 blockers. Our findings provide a foundation for future research targeting pyroptosis and its immune microenvironment to improve prognosis and responses to immunotherapy.
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spelling pubmed-82262592021-06-26 The Pyroptosis-Related Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Gastric Cancer Shao, Wei Yang, Zongcheng Fu, Yue Zheng, Lixin Liu, Fen Chai, Li Jia, Jihui Front Cell Dev Biol Cell and Developmental Biology Gastric cancer (GC) is one of the leading causes of cancer-related deaths and shows high levels of heterogeneity. The development of a specific prognostic model is important if we are to improve treatment strategies. Pyroptosis can arise in response to H. pylori, a primary carcinogen, and also in response to chemotherapy drugs. However, the prognostic evaluation of GC to pyroptosis is insufficient. Consensus clustering by pyroptosis-related regulators was used to classify 618 patients with GC from four GEO cohorts. Following Cox regression with differentially expressed genes, our prognosis model (PS-score) was built by LASSO-Cox analysis. The TCGA-STAD cohort was used as the validation set. ESTIMATE, CIBERSORTx, and EPIC were used to investigate the tumor microenvironment (TME). Immunotherapy cohorts by blocking PD1/PD-L1 were used to investigate the treatment response. The subtyping of GC based on pyroptosis-related regulators was able to classify patients according to different clinical traits and TME. The difference between the two subtypes identified in this study was used to develop a prognosis model which we named “PS-score.” The PS-score could predict the prognosis of patients with GC and his/her overall survival time. A low PS-score implies greater inflammatory cell infiltration and better response of immunotherapy by PD1/PD-L1 blockers. Our findings provide a foundation for future research targeting pyroptosis and its immune microenvironment to improve prognosis and responses to immunotherapy. Frontiers Media S.A. 2021-06-11 /pmc/articles/PMC8226259/ /pubmed/34179006 http://dx.doi.org/10.3389/fcell.2021.676485 Text en Copyright © 2021 Shao, Yang, Fu, Zheng, Liu, Chai and Jia. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Shao, Wei
Yang, Zongcheng
Fu, Yue
Zheng, Lixin
Liu, Fen
Chai, Li
Jia, Jihui
The Pyroptosis-Related Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Gastric Cancer
title The Pyroptosis-Related Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Gastric Cancer
title_full The Pyroptosis-Related Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Gastric Cancer
title_fullStr The Pyroptosis-Related Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Gastric Cancer
title_full_unstemmed The Pyroptosis-Related Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Gastric Cancer
title_short The Pyroptosis-Related Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Gastric Cancer
title_sort pyroptosis-related signature predicts prognosis and indicates immune microenvironment infiltration in gastric cancer
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226259/
https://www.ncbi.nlm.nih.gov/pubmed/34179006
http://dx.doi.org/10.3389/fcell.2021.676485
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