Integrative Analysis of DNA Methylation and Gene Expression Profiling Data Reveals Candidate Methylation-Regulated Genes in Hepatoblastoma

Jian-Yao Wang,1,* Jing Lao,2,* Yu Luo,3 Jing-Jie Guo,2 Hao Cheng,2 Hong-Yan Zhang,2 Jun Yao,4 Xiao-Peng Ma,1 Bin Wang1 1Department of General Surgery, Shenzhen Children’s Hospital, Shenzhen, 518026, Guangdong Province, People’s Republic of China; 2Shenzhen Children’s Hospital of Chin...

Full description

Bibliographic Details
Main Authors: Wang JY, Lao J, Luo Y, Guo JJ, Cheng H, Zhang HY, Yao J, Ma XP, Wang B
Format: Article
Language:English
Published: Dove Medical Press 2021-12-01
Series:International Journal of General Medicine
Subjects:
Online Access:https://www.dovepress.com/integrative-analysis-of-dna-methylation-and-gene-expression-profiling--peer-reviewed-fulltext-article-IJGM
_version_ 1818398644888403968
author Wang JY
Lao J
Luo Y
Guo JJ
Cheng H
Zhang HY
Yao J
Ma XP
Wang B
author_facet Wang JY
Lao J
Luo Y
Guo JJ
Cheng H
Zhang HY
Yao J
Ma XP
Wang B
author_sort Wang JY
collection DOAJ
description Jian-Yao Wang,1,* Jing Lao,2,* Yu Luo,3 Jing-Jie Guo,2 Hao Cheng,2 Hong-Yan Zhang,2 Jun Yao,4 Xiao-Peng Ma,1 Bin Wang1 1Department of General Surgery, Shenzhen Children’s Hospital, Shenzhen, 518026, Guangdong Province, People’s Republic of China; 2Shenzhen Children’s Hospital of China Medical University, Shenzhen, 518026, Guangdong Province, People’s Republic of China; 3Zhuhai Campus of Zunyi Medical University, Zhuhai, 519090, Guangdong Province, People’s Republic of China; 4Department of Gastroenterology, Jinan University of Medical Sciences, Shenzhen Municipal People’s Hospital, Shenzhen, 518020, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-Peng Ma; Bin Wang Tel +86-075583008073Email 1345012907@qq.com; szwb1967@126.comPurpose: This study aimed to identify novel methylation-regulated genes as diagnostic biomarkers and therapeutic targets for hepatoblastoma (HB).Materials and Methods: The DNA methylation data of 19 HB tumor samples and 10 normal liver samples from the GSE78732 dataset and gene expression profiling data of 53 HB tumor samples and 14 normal liver samples from the GSE131329 dataset and 31 HB tumor samples and 32 normal liver samples from the GSE133039 dataset were downloaded form the Gene Expression Omnibus database. Next, differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were identified. Venn diagrams were used to identify methylation-regulated genes. The VarElect online tool was selected to identify key methylation-regulated genes, and a protein–protein interaction (PPI) network was constructed to show the interactions among key methylation-regulated genes and DEGs. Finally, Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to investigate the potential regulatory mechanisms of key methylation-regulated genes.Results: A total of 457 DMGs and 1597 DEGs were identified between the HB and normal liver samples. After DMGs and DEGs overlapping, 22 hypomethylated and upregulated genes and 19 hypermethylated and downregulated genes in HB were screened. Survival analysis revealed that 13 methylation-regulated genes were associated with the prognosis of liver cancer. Moreover, SPP1, UHRF1, and HEY1 were selected as the key DNA methylation-regulated genes. The PPI network revealed that all of them could affect TP53, while both UHRF1 and HEY1 could influence BMP4. Enrichment analysis suggested that the DEGs were involved in TP53-related pathways, including the cell cycle and p53 signaling pathway. Finally, SPP1, UHRF1, and HEY1 were hypomethylated and upregulated in the HB samples compared with those in the normal liver samples.Conclusion: SPP1, UHRE1, and HEY1 may play important roles in HB and be used as biomarkers for its diagnosis and treatment.Keywords: DNA methylation, gene, hepatoblastoma, biomarker, tumor
first_indexed 2024-12-14T07:08:04Z
format Article
id doaj.art-628b7dad70024034b8013ab222664931
institution Directory Open Access Journal
issn 1178-7074
language English
last_indexed 2024-12-14T07:08:04Z
publishDate 2021-12-01
publisher Dove Medical Press
record_format Article
series International Journal of General Medicine
spelling doaj.art-628b7dad70024034b8013ab2226649312022-12-21T23:12:03ZengDove Medical PressInternational Journal of General Medicine1178-70742021-12-01Volume 149419943171230Integrative Analysis of DNA Methylation and Gene Expression Profiling Data Reveals Candidate Methylation-Regulated Genes in HepatoblastomaWang JYLao JLuo YGuo JJCheng HZhang HYYao JMa XPWang BJian-Yao Wang,1,* Jing Lao,2,* Yu Luo,3 Jing-Jie Guo,2 Hao Cheng,2 Hong-Yan Zhang,2 Jun Yao,4 Xiao-Peng Ma,1 Bin Wang1 1Department of General Surgery, Shenzhen Children’s Hospital, Shenzhen, 518026, Guangdong Province, People’s Republic of China; 2Shenzhen Children’s Hospital of China Medical University, Shenzhen, 518026, Guangdong Province, People’s Republic of China; 3Zhuhai Campus of Zunyi Medical University, Zhuhai, 519090, Guangdong Province, People’s Republic of China; 4Department of Gastroenterology, Jinan University of Medical Sciences, Shenzhen Municipal People’s Hospital, Shenzhen, 518020, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-Peng Ma; Bin Wang Tel +86-075583008073Email 1345012907@qq.com; szwb1967@126.comPurpose: This study aimed to identify novel methylation-regulated genes as diagnostic biomarkers and therapeutic targets for hepatoblastoma (HB).Materials and Methods: The DNA methylation data of 19 HB tumor samples and 10 normal liver samples from the GSE78732 dataset and gene expression profiling data of 53 HB tumor samples and 14 normal liver samples from the GSE131329 dataset and 31 HB tumor samples and 32 normal liver samples from the GSE133039 dataset were downloaded form the Gene Expression Omnibus database. Next, differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were identified. Venn diagrams were used to identify methylation-regulated genes. The VarElect online tool was selected to identify key methylation-regulated genes, and a protein–protein interaction (PPI) network was constructed to show the interactions among key methylation-regulated genes and DEGs. Finally, Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to investigate the potential regulatory mechanisms of key methylation-regulated genes.Results: A total of 457 DMGs and 1597 DEGs were identified between the HB and normal liver samples. After DMGs and DEGs overlapping, 22 hypomethylated and upregulated genes and 19 hypermethylated and downregulated genes in HB were screened. Survival analysis revealed that 13 methylation-regulated genes were associated with the prognosis of liver cancer. Moreover, SPP1, UHRF1, and HEY1 were selected as the key DNA methylation-regulated genes. The PPI network revealed that all of them could affect TP53, while both UHRF1 and HEY1 could influence BMP4. Enrichment analysis suggested that the DEGs were involved in TP53-related pathways, including the cell cycle and p53 signaling pathway. Finally, SPP1, UHRF1, and HEY1 were hypomethylated and upregulated in the HB samples compared with those in the normal liver samples.Conclusion: SPP1, UHRE1, and HEY1 may play important roles in HB and be used as biomarkers for its diagnosis and treatment.Keywords: DNA methylation, gene, hepatoblastoma, biomarker, tumorhttps://www.dovepress.com/integrative-analysis-of-dna-methylation-and-gene-expression-profiling--peer-reviewed-fulltext-article-IJGMdna methylationgenehepatoblastomabiomarkertumor
spellingShingle Wang JY
Lao J
Luo Y
Guo JJ
Cheng H
Zhang HY
Yao J
Ma XP
Wang B
Integrative Analysis of DNA Methylation and Gene Expression Profiling Data Reveals Candidate Methylation-Regulated Genes in Hepatoblastoma
International Journal of General Medicine
dna methylation
gene
hepatoblastoma
biomarker
tumor
title Integrative Analysis of DNA Methylation and Gene Expression Profiling Data Reveals Candidate Methylation-Regulated Genes in Hepatoblastoma
title_full Integrative Analysis of DNA Methylation and Gene Expression Profiling Data Reveals Candidate Methylation-Regulated Genes in Hepatoblastoma
title_fullStr Integrative Analysis of DNA Methylation and Gene Expression Profiling Data Reveals Candidate Methylation-Regulated Genes in Hepatoblastoma
title_full_unstemmed Integrative Analysis of DNA Methylation and Gene Expression Profiling Data Reveals Candidate Methylation-Regulated Genes in Hepatoblastoma
title_short Integrative Analysis of DNA Methylation and Gene Expression Profiling Data Reveals Candidate Methylation-Regulated Genes in Hepatoblastoma
title_sort integrative analysis of dna methylation and gene expression profiling data reveals candidate methylation regulated genes in hepatoblastoma
topic dna methylation
gene
hepatoblastoma
biomarker
tumor
url https://www.dovepress.com/integrative-analysis-of-dna-methylation-and-gene-expression-profiling--peer-reviewed-fulltext-article-IJGM
work_keys_str_mv AT wangjy integrativeanalysisofdnamethylationandgeneexpressionprofilingdatarevealscandidatemethylationregulatedgenesinhepatoblastoma
AT laoj integrativeanalysisofdnamethylationandgeneexpressionprofilingdatarevealscandidatemethylationregulatedgenesinhepatoblastoma
AT luoy integrativeanalysisofdnamethylationandgeneexpressionprofilingdatarevealscandidatemethylationregulatedgenesinhepatoblastoma
AT guojj integrativeanalysisofdnamethylationandgeneexpressionprofilingdatarevealscandidatemethylationregulatedgenesinhepatoblastoma
AT chengh integrativeanalysisofdnamethylationandgeneexpressionprofilingdatarevealscandidatemethylationregulatedgenesinhepatoblastoma
AT zhanghy integrativeanalysisofdnamethylationandgeneexpressionprofilingdatarevealscandidatemethylationregulatedgenesinhepatoblastoma
AT yaoj integrativeanalysisofdnamethylationandgeneexpressionprofilingdatarevealscandidatemethylationregulatedgenesinhepatoblastoma
AT maxp integrativeanalysisofdnamethylationandgeneexpressionprofilingdatarevealscandidatemethylationregulatedgenesinhepatoblastoma
AT wangb integrativeanalysisofdnamethylationandgeneexpressionprofilingdatarevealscandidatemethylationregulatedgenesinhepatoblastoma