Identification of key pathways and potential biomarkers for intrahepatic cholangiocarcinoma based on integrated bioinformatics and evaluation of their diagnostic value

Objective To identify the key pathways and potential biomarkers with diagnotic value for the development of intrahepatic cholangiocarcinoma (ICC) by integrating bioinformatics analysis. Methods We downloaded 3 high-quality datasets of ICC gene microarray (GSE26566, GSE32879 and GSE45001) from Gene E...

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Main Authors: LIU Bo, FU Tingting, GUO Xiaodong, HE Ping, WANG Honglin
Format: Article
Language:zho
Published: Editorial Office of Journal of Third Military Medical University 2021-05-01
Series:Di-san junyi daxue xuebao
Subjects:
Online Access:http://aammt.tmmu.edu.cn/Upload/rhtml/202011021.htm
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author LIU Bo
FU Tingting
GUO Xiaodong
HE Ping
WANG Honglin
author_facet LIU Bo
FU Tingting
GUO Xiaodong
HE Ping
WANG Honglin
author_sort LIU Bo
collection DOAJ
description Objective To identify the key pathways and potential biomarkers with diagnotic value for the development of intrahepatic cholangiocarcinoma (ICC) by integrating bioinformatics analysis. Methods We downloaded 3 high-quality datasets of ICC gene microarray (GSE26566, GSE32879 and GSE45001) from Gene Expression Omnibus (GEO) and the high-throughput sequencing data of cholangiocarcinoma (CCA) from the Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were screened using the Limma package in R software; Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed with Cluster Profiler package. Protein-protein interaction (PPI) network analysis of DEGs was subsequently carried out using the Search Tool for the Retrieval of Interacting Genes (STRING) database and subsequently visualized with Cytoscape. In addition, the transcriptional expression of hub genes was further verified by Gene Expression Profiling Interactive Analysis (GEPIA), and their diagnostic value was assessed by receiver operating characteristic (ROC) curve. Finally, the methylation level of the hub genes was determined using Diseasemeth 2.0. Results In total, 382 DEGs were screened and validated, including 90 up-regulated and 292 down-regulated genes. The up-regulated genes were noticeably enriched in PI3K-Akt signaling pathway, while the down-regulated in the carbon metabolism pathway. A PPI network was constructed with 289 nodes, and 6 hub genes were identified by PPI analysis: PRSS23, LGALS1, VCAN, COL5A1, ITGB1 and EHHADH. ROC curve results showed that all the hub genes distinguished tumor tissues from non-tumorous tissues. Conclusion Six hub genes are identified by integrative bioinformatics analysis, which may be potential molecular biomarkers for early diagnosis of ICC.
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spelling doaj.art-4240093e58aa45119d44962a2e2135982022-12-21T17:23:12ZzhoEditorial Office of Journal of Third Military Medical UniversityDi-san junyi daxue xuebao1000-54042021-05-01431091592210.16016/j.1000-5404.202011021Identification of key pathways and potential biomarkers for intrahepatic cholangiocarcinoma based on integrated bioinformatics and evaluation of their diagnostic valueLIU Bo0FU Tingting1GUO Xiaodong2HE Ping3WANG Honglin4Department of Hepatopancreatobiliary Surgery, the Third Affiliated Hospital of Chengdu Medical College (Chengdu Pidu District People's Hospital), Chengdu, Sichuan Province, 611730Department of Nosocomial Infection Control, the Third Affiliated Hospital of Chengdu Medical College (Chengdu Pidu District People's Hospital), Chengdu, Sichuan Province, 611730Department of Hepatopancreatobiliary Surgery, the Third Affiliated Hospital of Chengdu Medical College (Chengdu Pidu District People's Hospital), Chengdu, Sichuan Province, 611730Department of Hepatopancreatobiliary Surgery, the Third Affiliated Hospital of Chengdu Medical College (Chengdu Pidu District People's Hospital), Chengdu, Sichuan Province, 611730 Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China Objective To identify the key pathways and potential biomarkers with diagnotic value for the development of intrahepatic cholangiocarcinoma (ICC) by integrating bioinformatics analysis. Methods We downloaded 3 high-quality datasets of ICC gene microarray (GSE26566, GSE32879 and GSE45001) from Gene Expression Omnibus (GEO) and the high-throughput sequencing data of cholangiocarcinoma (CCA) from the Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were screened using the Limma package in R software; Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed with Cluster Profiler package. Protein-protein interaction (PPI) network analysis of DEGs was subsequently carried out using the Search Tool for the Retrieval of Interacting Genes (STRING) database and subsequently visualized with Cytoscape. In addition, the transcriptional expression of hub genes was further verified by Gene Expression Profiling Interactive Analysis (GEPIA), and their diagnostic value was assessed by receiver operating characteristic (ROC) curve. Finally, the methylation level of the hub genes was determined using Diseasemeth 2.0. Results In total, 382 DEGs were screened and validated, including 90 up-regulated and 292 down-regulated genes. The up-regulated genes were noticeably enriched in PI3K-Akt signaling pathway, while the down-regulated in the carbon metabolism pathway. A PPI network was constructed with 289 nodes, and 6 hub genes were identified by PPI analysis: PRSS23, LGALS1, VCAN, COL5A1, ITGB1 and EHHADH. ROC curve results showed that all the hub genes distinguished tumor tissues from non-tumorous tissues. Conclusion Six hub genes are identified by integrative bioinformatics analysis, which may be potential molecular biomarkers for early diagnosis of ICC.http://aammt.tmmu.edu.cn/Upload/rhtml/202011021.htmcholangiocarcinomabioinformaticsbiomarkergene expression omnibuscancer genome atlas database
spellingShingle LIU Bo
FU Tingting
GUO Xiaodong
HE Ping
WANG Honglin
Identification of key pathways and potential biomarkers for intrahepatic cholangiocarcinoma based on integrated bioinformatics and evaluation of their diagnostic value
Di-san junyi daxue xuebao
cholangiocarcinoma
bioinformatics
biomarker
gene expression omnibus
cancer genome atlas database
title Identification of key pathways and potential biomarkers for intrahepatic cholangiocarcinoma based on integrated bioinformatics and evaluation of their diagnostic value
title_full Identification of key pathways and potential biomarkers for intrahepatic cholangiocarcinoma based on integrated bioinformatics and evaluation of their diagnostic value
title_fullStr Identification of key pathways and potential biomarkers for intrahepatic cholangiocarcinoma based on integrated bioinformatics and evaluation of their diagnostic value
title_full_unstemmed Identification of key pathways and potential biomarkers for intrahepatic cholangiocarcinoma based on integrated bioinformatics and evaluation of their diagnostic value
title_short Identification of key pathways and potential biomarkers for intrahepatic cholangiocarcinoma based on integrated bioinformatics and evaluation of their diagnostic value
title_sort identification of key pathways and potential biomarkers for intrahepatic cholangiocarcinoma based on integrated bioinformatics and evaluation of their diagnostic value
topic cholangiocarcinoma
bioinformatics
biomarker
gene expression omnibus
cancer genome atlas database
url http://aammt.tmmu.edu.cn/Upload/rhtml/202011021.htm
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