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A Ferroptosis and Pyroptosis Molecular Subtype-Related Signature Applicable for Prognosis and Immune Microenvironment Estimation in Hepatocellular Carcinoma

Background: Due to the heterogeneity of tumors and the complexity of the immune microenvironment, the specific role of ferroptosis and pyroptosis in hepatocellular carcinoma (HCC) is not fully understood, especially its impact on prognosis. Methods: The training set (n = 609, merged by TCGA and GSE1...

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Autores principales: Huo, Junyu, Cai, Jinzhen, Guan, Ge, Liu, Huan, Wu, Liqun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634890/
https://www.ncbi.nlm.nih.gov/pubmed/34869350
http://dx.doi.org/10.3389/fcell.2021.761839
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author Huo, Junyu
Cai, Jinzhen
Guan, Ge
Liu, Huan
Wu, Liqun
author_facet Huo, Junyu
Cai, Jinzhen
Guan, Ge
Liu, Huan
Wu, Liqun
author_sort Huo, Junyu
collection PubMed
description Background: Due to the heterogeneity of tumors and the complexity of the immune microenvironment, the specific role of ferroptosis and pyroptosis in hepatocellular carcinoma (HCC) is not fully understood, especially its impact on prognosis. Methods: The training set (n = 609, merged by TCGA and GSE14520) was clustered into three subtypes (C1, C2, and C3) based on the prognosis-related genes associated with ferroptosis and pyroptosis. The intersecting differentially expressed genes (DEGs) among C1, C2, and C3 were used in univariate Cox and LASSO penalized Cox regression analysis for the construction of the risk score. The median risk score served as the unified cutoff to divide patients into high- and low-risk groups. Results: Internal (TCGA, n = 370; GSE14520, n = 239) and external validation (ICGC, n = 231) suggested that the 12-gene risk score had high accuracy in predicting the OS, DSS, DFS, PFS, and RFS of HCC. As an independent prognostic indicator, the risk score could be applicable for patients with different clinical features tested by subgroup (n = 26) survival analysis. In the high-risk patients with a lower infiltration abundance of activated B cells, activated CD8 T cells, eosinophils, and type I T helper cells and a higher infiltration abundance of immature dendritic cells, the cytolytic activity, HLA, inflammation promotion, and type I IFN response in the high-risk group were weaker. The TP53 mutation rate, TMB, and CSC characteristics in the high-risk group were significantly higher than those in the low-risk group. Low-risk patients have active metabolic activity and a more robust immune response. The high- and low-risk groups differed significantly in histology grade, vascular tumor cell type, AFP, new tumor event after initial treatment, main tumor size, cirrhosis, TNM stage, BCLC stage, and CLIP score. Conclusion: The ferroptosis and pyroptosis molecular subtype-related signature identified and validated in this work is applicable for prognosis prediction, immune microenvironment estimation, stem cell characteristics, and clinical feature assessment in HCC.
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spelling pubmed-86348902021-12-02 A Ferroptosis and Pyroptosis Molecular Subtype-Related Signature Applicable for Prognosis and Immune Microenvironment Estimation in Hepatocellular Carcinoma Huo, Junyu Cai, Jinzhen Guan, Ge Liu, Huan Wu, Liqun Front Cell Dev Biol Cell and Developmental Biology Background: Due to the heterogeneity of tumors and the complexity of the immune microenvironment, the specific role of ferroptosis and pyroptosis in hepatocellular carcinoma (HCC) is not fully understood, especially its impact on prognosis. Methods: The training set (n = 609, merged by TCGA and GSE14520) was clustered into three subtypes (C1, C2, and C3) based on the prognosis-related genes associated with ferroptosis and pyroptosis. The intersecting differentially expressed genes (DEGs) among C1, C2, and C3 were used in univariate Cox and LASSO penalized Cox regression analysis for the construction of the risk score. The median risk score served as the unified cutoff to divide patients into high- and low-risk groups. Results: Internal (TCGA, n = 370; GSE14520, n = 239) and external validation (ICGC, n = 231) suggested that the 12-gene risk score had high accuracy in predicting the OS, DSS, DFS, PFS, and RFS of HCC. As an independent prognostic indicator, the risk score could be applicable for patients with different clinical features tested by subgroup (n = 26) survival analysis. In the high-risk patients with a lower infiltration abundance of activated B cells, activated CD8 T cells, eosinophils, and type I T helper cells and a higher infiltration abundance of immature dendritic cells, the cytolytic activity, HLA, inflammation promotion, and type I IFN response in the high-risk group were weaker. The TP53 mutation rate, TMB, and CSC characteristics in the high-risk group were significantly higher than those in the low-risk group. Low-risk patients have active metabolic activity and a more robust immune response. The high- and low-risk groups differed significantly in histology grade, vascular tumor cell type, AFP, new tumor event after initial treatment, main tumor size, cirrhosis, TNM stage, BCLC stage, and CLIP score. Conclusion: The ferroptosis and pyroptosis molecular subtype-related signature identified and validated in this work is applicable for prognosis prediction, immune microenvironment estimation, stem cell characteristics, and clinical feature assessment in HCC. Frontiers Media S.A. 2021-11-15 /pmc/articles/PMC8634890/ /pubmed/34869350 http://dx.doi.org/10.3389/fcell.2021.761839 Text en Copyright © 2021 Huo, Cai, Guan, Liu and Wu. 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
Huo, Junyu
Cai, Jinzhen
Guan, Ge
Liu, Huan
Wu, Liqun
A Ferroptosis and Pyroptosis Molecular Subtype-Related Signature Applicable for Prognosis and Immune Microenvironment Estimation in Hepatocellular Carcinoma
title A Ferroptosis and Pyroptosis Molecular Subtype-Related Signature Applicable for Prognosis and Immune Microenvironment Estimation in Hepatocellular Carcinoma
title_full A Ferroptosis and Pyroptosis Molecular Subtype-Related Signature Applicable for Prognosis and Immune Microenvironment Estimation in Hepatocellular Carcinoma
title_fullStr A Ferroptosis and Pyroptosis Molecular Subtype-Related Signature Applicable for Prognosis and Immune Microenvironment Estimation in Hepatocellular Carcinoma
title_full_unstemmed A Ferroptosis and Pyroptosis Molecular Subtype-Related Signature Applicable for Prognosis and Immune Microenvironment Estimation in Hepatocellular Carcinoma
title_short A Ferroptosis and Pyroptosis Molecular Subtype-Related Signature Applicable for Prognosis and Immune Microenvironment Estimation in Hepatocellular Carcinoma
title_sort ferroptosis and pyroptosis molecular subtype-related signature applicable for prognosis and immune microenvironment estimation in hepatocellular carcinoma
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634890/
https://www.ncbi.nlm.nih.gov/pubmed/34869350
http://dx.doi.org/10.3389/fcell.2021.761839
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