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Prognostic and immune correlation evaluation of a novel cuproptosis-related genes signature in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the world’s malignant tumors with high morbidity and mortality. Cuproptosis is a novel form of cell death. However, the prognostic evaluation and immune relevance of cuproptosis-related genes (CRGs) in HCC are largely unknown. In our study, we constructed a p...

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Autores principales: Zhou, Zheng, Zhou, Yusong, Liu, Dongbo, Yang, Qingping, Tang, Mengjie, Liu, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9795230/
https://www.ncbi.nlm.nih.gov/pubmed/36588699
http://dx.doi.org/10.3389/fphar.2022.1074123
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author Zhou, Zheng
Zhou, Yusong
Liu, Dongbo
Yang, Qingping
Tang, Mengjie
Liu, Wei
author_facet Zhou, Zheng
Zhou, Yusong
Liu, Dongbo
Yang, Qingping
Tang, Mengjie
Liu, Wei
author_sort Zhou, Zheng
collection PubMed
description Hepatocellular carcinoma (HCC) is one of the world’s malignant tumors with high morbidity and mortality. Cuproptosis is a novel form of cell death. However, the prognostic evaluation and immune relevance of cuproptosis-related genes (CRGs) in HCC are largely unknown. In our study, we constructed a prognostic model of CRGs in HCC and performed immune infiltration, functional analysis, immune checkpoint and drug sensitivity analysis. Systematically elaborated the prognostic and immune correlation of CRGs in HCC. The results showed that 15 CRGs were up-regulated or down-regulated in HCC, and the mutation frequency of CRGs reached 10.33% in HCC, with CDKN2A having the highest mutation frequency. These 19 CRGs were mainly involved in the mitochondrion, immune response and metabolic pathways. Five selected genes (CDKN2A, DLAT, DLST, GLS, PDHA1) were involved in constructing a prognostic CRGs model that enables the overall survival in HCC patients to be predicted with moderate to high accuracy. Prognostic CRGs, especially CDKN2A, the independent factor of HCC prognosis, may be closely associated with immune-cell infiltration, tumor mutation burden (TMB), microsatellite instability(MSI), and immune checkpoints. CD274, CTLA4, LAG3, PDCD1, PDCD1LG2 and SIGLEC15 may be identified as potential therapeutic targets and CD274 correlated highly with prognostic genes. Quantitative Real-Time PCR (qRT-PCR) and immunohistochemical were performed to validate the mRNA and protein expression levels of CDKN2A in adjacent normal tissues and HCC tissues, and the results were consistent with gene difference analysis. In conclusion, CRGs, especially CDKN2A, may serve as potential prognostic predictors in HCC patients and provide novel insights into cancer therapy.
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spelling pubmed-97952302022-12-29 Prognostic and immune correlation evaluation of a novel cuproptosis-related genes signature in hepatocellular carcinoma Zhou, Zheng Zhou, Yusong Liu, Dongbo Yang, Qingping Tang, Mengjie Liu, Wei Front Pharmacol Pharmacology Hepatocellular carcinoma (HCC) is one of the world’s malignant tumors with high morbidity and mortality. Cuproptosis is a novel form of cell death. However, the prognostic evaluation and immune relevance of cuproptosis-related genes (CRGs) in HCC are largely unknown. In our study, we constructed a prognostic model of CRGs in HCC and performed immune infiltration, functional analysis, immune checkpoint and drug sensitivity analysis. Systematically elaborated the prognostic and immune correlation of CRGs in HCC. The results showed that 15 CRGs were up-regulated or down-regulated in HCC, and the mutation frequency of CRGs reached 10.33% in HCC, with CDKN2A having the highest mutation frequency. These 19 CRGs were mainly involved in the mitochondrion, immune response and metabolic pathways. Five selected genes (CDKN2A, DLAT, DLST, GLS, PDHA1) were involved in constructing a prognostic CRGs model that enables the overall survival in HCC patients to be predicted with moderate to high accuracy. Prognostic CRGs, especially CDKN2A, the independent factor of HCC prognosis, may be closely associated with immune-cell infiltration, tumor mutation burden (TMB), microsatellite instability(MSI), and immune checkpoints. CD274, CTLA4, LAG3, PDCD1, PDCD1LG2 and SIGLEC15 may be identified as potential therapeutic targets and CD274 correlated highly with prognostic genes. Quantitative Real-Time PCR (qRT-PCR) and immunohistochemical were performed to validate the mRNA and protein expression levels of CDKN2A in adjacent normal tissues and HCC tissues, and the results were consistent with gene difference analysis. In conclusion, CRGs, especially CDKN2A, may serve as potential prognostic predictors in HCC patients and provide novel insights into cancer therapy. Frontiers Media S.A. 2022-12-14 /pmc/articles/PMC9795230/ /pubmed/36588699 http://dx.doi.org/10.3389/fphar.2022.1074123 Text en Copyright © 2022 Zhou, Zhou, Liu, Yang, Tang and Liu. 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 Pharmacology
Zhou, Zheng
Zhou, Yusong
Liu, Dongbo
Yang, Qingping
Tang, Mengjie
Liu, Wei
Prognostic and immune correlation evaluation of a novel cuproptosis-related genes signature in hepatocellular carcinoma
title Prognostic and immune correlation evaluation of a novel cuproptosis-related genes signature in hepatocellular carcinoma
title_full Prognostic and immune correlation evaluation of a novel cuproptosis-related genes signature in hepatocellular carcinoma
title_fullStr Prognostic and immune correlation evaluation of a novel cuproptosis-related genes signature in hepatocellular carcinoma
title_full_unstemmed Prognostic and immune correlation evaluation of a novel cuproptosis-related genes signature in hepatocellular carcinoma
title_short Prognostic and immune correlation evaluation of a novel cuproptosis-related genes signature in hepatocellular carcinoma
title_sort prognostic and immune correlation evaluation of a novel cuproptosis-related genes signature in hepatocellular carcinoma
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9795230/
https://www.ncbi.nlm.nih.gov/pubmed/36588699
http://dx.doi.org/10.3389/fphar.2022.1074123
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