Cargando…

Mining prognostic markers of Asian hepatocellular carcinoma patients based on the apoptosis-related genes

BACKGROUND: Apoptosis-related genes(Args)play an essential role in the occurrence and progression of hepatocellular carcinoma(HCC). However, few studies have focused on the prognostic significance of Args in HCC. In the study, we aim to explore an efficient prognostic model of Asian HCC patients bas...

Descripción completa

Detalles Bibliográficos
Autores principales: Yan, Junbin, Cao, Jielu, Chen, Zhiyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891020/
https://www.ncbi.nlm.nih.gov/pubmed/33602168
http://dx.doi.org/10.1186/s12885-021-07886-6
_version_ 1783652617041215488
author Yan, Junbin
Cao, Jielu
Chen, Zhiyun
author_facet Yan, Junbin
Cao, Jielu
Chen, Zhiyun
author_sort Yan, Junbin
collection PubMed
description BACKGROUND: Apoptosis-related genes(Args)play an essential role in the occurrence and progression of hepatocellular carcinoma(HCC). However, few studies have focused on the prognostic significance of Args in HCC. In the study, we aim to explore an efficient prognostic model of Asian HCC patients based on the Args. METHODS: We downloaded mRNA expression profiles and corresponding clinical data of Asian HCC patients from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The Args were collected from Deathbase, a database related to cell death, combined with the research results of GeneCards、National Center for Biotechnology Information (NCBI) databases and a lot of literature. We used Wilcoxon-test and univariate Cox analysis to screen the differential expressed genes (DEGs) and the prognostic related genes (PRGs) of HCC. The intersection genes of DEGs and PGGs were seen as crucial Args of HCC. The prognostic model of Asian HCC patients was constructed by least absolute shrinkage and selection operator (lasso)- proportional hazards model (Cox) regression analysis. Kaplan-Meier curve, Principal Component Analysis (PCA) analysis, t-distributed Stochastic Neighbor Embedding (t-SNE) analysis, risk score curve, receiver operating characteristic (ROC) curve, and the HCC data of ICGC database and the data of Asian HCC patients of Kaplan-Meier plotter database were used to verify the model. RESULTS: A total of 20 of 56 Args were differentially expressed between HCC and adjacent normal tissues (p < 0.05). Univariate Cox regression analysis showed that 10 of 56 Args were associated with survival time and survival status of HCC patients (p < 0.05). There are seven overlapping genes of these 20 and 10 genes, including BAK1, BAX, BNIP3, CRADD, CSE1L, FAS, and SH3GLB1. Through Lasso-Cox analysis, an HCC prognostic model composed of BAK1, BNIP3, CSE1L, and FAS was constructed. Kaplan-Meier curve, PCA, t-SNE analysis, risk score curve, ROC curve, and secondary verification of ICGC database and Kaplan-Meier plotter database all support the reliability of the model. CONCLUSIONS: Lasso-Cox regression analysis identified a 4-gene prognostic model, which integrates clinical and gene expression and has a good effect. The expression of Args is related to the prognosis of HCC patients, but the specific mechanism remains to be further verified. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-07886-6.
format Online
Article
Text
id pubmed-7891020
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-78910202021-02-22 Mining prognostic markers of Asian hepatocellular carcinoma patients based on the apoptosis-related genes Yan, Junbin Cao, Jielu Chen, Zhiyun BMC Cancer Research Article BACKGROUND: Apoptosis-related genes(Args)play an essential role in the occurrence and progression of hepatocellular carcinoma(HCC). However, few studies have focused on the prognostic significance of Args in HCC. In the study, we aim to explore an efficient prognostic model of Asian HCC patients based on the Args. METHODS: We downloaded mRNA expression profiles and corresponding clinical data of Asian HCC patients from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The Args were collected from Deathbase, a database related to cell death, combined with the research results of GeneCards、National Center for Biotechnology Information (NCBI) databases and a lot of literature. We used Wilcoxon-test and univariate Cox analysis to screen the differential expressed genes (DEGs) and the prognostic related genes (PRGs) of HCC. The intersection genes of DEGs and PGGs were seen as crucial Args of HCC. The prognostic model of Asian HCC patients was constructed by least absolute shrinkage and selection operator (lasso)- proportional hazards model (Cox) regression analysis. Kaplan-Meier curve, Principal Component Analysis (PCA) analysis, t-distributed Stochastic Neighbor Embedding (t-SNE) analysis, risk score curve, receiver operating characteristic (ROC) curve, and the HCC data of ICGC database and the data of Asian HCC patients of Kaplan-Meier plotter database were used to verify the model. RESULTS: A total of 20 of 56 Args were differentially expressed between HCC and adjacent normal tissues (p < 0.05). Univariate Cox regression analysis showed that 10 of 56 Args were associated with survival time and survival status of HCC patients (p < 0.05). There are seven overlapping genes of these 20 and 10 genes, including BAK1, BAX, BNIP3, CRADD, CSE1L, FAS, and SH3GLB1. Through Lasso-Cox analysis, an HCC prognostic model composed of BAK1, BNIP3, CSE1L, and FAS was constructed. Kaplan-Meier curve, PCA, t-SNE analysis, risk score curve, ROC curve, and secondary verification of ICGC database and Kaplan-Meier plotter database all support the reliability of the model. CONCLUSIONS: Lasso-Cox regression analysis identified a 4-gene prognostic model, which integrates clinical and gene expression and has a good effect. The expression of Args is related to the prognosis of HCC patients, but the specific mechanism remains to be further verified. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-07886-6. BioMed Central 2021-02-18 /pmc/articles/PMC7891020/ /pubmed/33602168 http://dx.doi.org/10.1186/s12885-021-07886-6 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 Article
Yan, Junbin
Cao, Jielu
Chen, Zhiyun
Mining prognostic markers of Asian hepatocellular carcinoma patients based on the apoptosis-related genes
title Mining prognostic markers of Asian hepatocellular carcinoma patients based on the apoptosis-related genes
title_full Mining prognostic markers of Asian hepatocellular carcinoma patients based on the apoptosis-related genes
title_fullStr Mining prognostic markers of Asian hepatocellular carcinoma patients based on the apoptosis-related genes
title_full_unstemmed Mining prognostic markers of Asian hepatocellular carcinoma patients based on the apoptosis-related genes
title_short Mining prognostic markers of Asian hepatocellular carcinoma patients based on the apoptosis-related genes
title_sort mining prognostic markers of asian hepatocellular carcinoma patients based on the apoptosis-related genes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891020/
https://www.ncbi.nlm.nih.gov/pubmed/33602168
http://dx.doi.org/10.1186/s12885-021-07886-6
work_keys_str_mv AT yanjunbin miningprognosticmarkersofasianhepatocellularcarcinomapatientsbasedontheapoptosisrelatedgenes
AT caojielu miningprognosticmarkersofasianhepatocellularcarcinomapatientsbasedontheapoptosisrelatedgenes
AT chenzhiyun miningprognosticmarkersofasianhepatocellularcarcinomapatientsbasedontheapoptosisrelatedgenes