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A prognostic model for hepatocellular carcinoma based on apoptosis-related genes

BACKGROUND: Dysregulation of the balance between proliferation and apoptosis is the basis for human hepatocarcinogenesis. In many malignant tumors, such as hepatocellular carcinoma (HCC), there is a correlation between apoptotic dysregulation and poor prognosis. However, the prognostic values of apo...

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Autores principales: Liu, Renjie, Wang, Guifu, Zhang, Chi, Bai, Dousheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955636/
https://www.ncbi.nlm.nih.gov/pubmed/33712023
http://dx.doi.org/10.1186/s12957-021-02175-9
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author Liu, Renjie
Wang, Guifu
Zhang, Chi
Bai, Dousheng
author_facet Liu, Renjie
Wang, Guifu
Zhang, Chi
Bai, Dousheng
author_sort Liu, Renjie
collection PubMed
description BACKGROUND: Dysregulation of the balance between proliferation and apoptosis is the basis for human hepatocarcinogenesis. In many malignant tumors, such as hepatocellular carcinoma (HCC), there is a correlation between apoptotic dysregulation and poor prognosis. However, the prognostic values of apoptosis-related genes (ARGs) in HCC have not been elucidated. METHODS: To screen for differentially expressed ARGs, the expression levels of 161 ARGs from The Cancer Genome Atlas (TCGA) database (https://cancergenome.nih.gov/) were analyzed. Gene Ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to evaluate the underlying molecular mechanisms of differentially expressed ARGs in HCC. The prognostic values of ARGs were established using Cox regression, and subsequently, a prognostic risk model for scoring patients was developed. Kaplan–Meier (K-M) and receiver operating characteristic (ROC) curves were plotted to determine the prognostic value of the model. RESULTS: Compared with normal tissues, 43 highly upregulated and 8 downregulated ARGs in HCC tissues were screened. GO analysis results revealed that these 51 genes are indeed related to the apoptosis function. KEGG analysis revealed that these 51 genes were correlated with MAPK, P53, TNF, and PI3K-AKT signaling pathways, while Cox regression revealed that 5 ARGs (PPP2R5B, SQSTM1, TOP2A, BMF, and LGALS3) were associated with prognosis and were, therefore, obtained to develop the prognostic model. Based on the median risk scores, patients were categorized into high-risk and low-risk groups. Patients in the low-risk groups exhibited significantly elevated 2-year or 5-year survival probabilities (p < 0.0001). The risk model had a better clinical potency than the other clinical characteristics, with the area under the ROC curve (AUC = 0.741). The prognosis of HCC patients was established from a plotted nomogram. CONCLUSION: Based on the differential expression of ARGs, we established a novel risk model for predicting HCC prognosis. This model can also be used to inform the individualized treatment of HCC patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12957-021-02175-9.
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spelling pubmed-79556362021-03-15 A prognostic model for hepatocellular carcinoma based on apoptosis-related genes Liu, Renjie Wang, Guifu Zhang, Chi Bai, Dousheng World J Surg Oncol Research BACKGROUND: Dysregulation of the balance between proliferation and apoptosis is the basis for human hepatocarcinogenesis. In many malignant tumors, such as hepatocellular carcinoma (HCC), there is a correlation between apoptotic dysregulation and poor prognosis. However, the prognostic values of apoptosis-related genes (ARGs) in HCC have not been elucidated. METHODS: To screen for differentially expressed ARGs, the expression levels of 161 ARGs from The Cancer Genome Atlas (TCGA) database (https://cancergenome.nih.gov/) were analyzed. Gene Ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to evaluate the underlying molecular mechanisms of differentially expressed ARGs in HCC. The prognostic values of ARGs were established using Cox regression, and subsequently, a prognostic risk model for scoring patients was developed. Kaplan–Meier (K-M) and receiver operating characteristic (ROC) curves were plotted to determine the prognostic value of the model. RESULTS: Compared with normal tissues, 43 highly upregulated and 8 downregulated ARGs in HCC tissues were screened. GO analysis results revealed that these 51 genes are indeed related to the apoptosis function. KEGG analysis revealed that these 51 genes were correlated with MAPK, P53, TNF, and PI3K-AKT signaling pathways, while Cox regression revealed that 5 ARGs (PPP2R5B, SQSTM1, TOP2A, BMF, and LGALS3) were associated with prognosis and were, therefore, obtained to develop the prognostic model. Based on the median risk scores, patients were categorized into high-risk and low-risk groups. Patients in the low-risk groups exhibited significantly elevated 2-year or 5-year survival probabilities (p < 0.0001). The risk model had a better clinical potency than the other clinical characteristics, with the area under the ROC curve (AUC = 0.741). The prognosis of HCC patients was established from a plotted nomogram. CONCLUSION: Based on the differential expression of ARGs, we established a novel risk model for predicting HCC prognosis. This model can also be used to inform the individualized treatment of HCC patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12957-021-02175-9. BioMed Central 2021-03-12 /pmc/articles/PMC7955636/ /pubmed/33712023 http://dx.doi.org/10.1186/s12957-021-02175-9 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Liu, Renjie
Wang, Guifu
Zhang, Chi
Bai, Dousheng
A prognostic model for hepatocellular carcinoma based on apoptosis-related genes
title A prognostic model for hepatocellular carcinoma based on apoptosis-related genes
title_full A prognostic model for hepatocellular carcinoma based on apoptosis-related genes
title_fullStr A prognostic model for hepatocellular carcinoma based on apoptosis-related genes
title_full_unstemmed A prognostic model for hepatocellular carcinoma based on apoptosis-related genes
title_short A prognostic model for hepatocellular carcinoma based on apoptosis-related genes
title_sort prognostic model for hepatocellular carcinoma based on apoptosis-related genes
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955636/
https://www.ncbi.nlm.nih.gov/pubmed/33712023
http://dx.doi.org/10.1186/s12957-021-02175-9
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