Identification of Seven Aberrantly Methylated and Expressed Genes in Adrenocortical Carcinoma

Background: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an unfavorable prognosis and limited treatment options. Nevertheless, no clinically applicable molecular markers have been identified for the progression of ACCs. DNA methylation alterations were found to contribute to th...

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Main Authors: He Xiao, Weixiang He, Ping Chen, Deqiang Xu, Guang Zeng, Zhuo Li, Mingliu Huang, Xinghuan Wang, Michael E. DiSanto, Xinhua Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-07-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fendo.2019.00472/full
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author He Xiao
Weixiang He
Ping Chen
Deqiang Xu
Guang Zeng
Zhuo Li
Zhuo Li
Zhuo Li
Zhuo Li
Zhuo Li
Mingliu Huang
Xinghuan Wang
Michael E. DiSanto
Xinhua Zhang
author_facet He Xiao
Weixiang He
Ping Chen
Deqiang Xu
Guang Zeng
Zhuo Li
Zhuo Li
Zhuo Li
Zhuo Li
Zhuo Li
Mingliu Huang
Xinghuan Wang
Michael E. DiSanto
Xinhua Zhang
author_sort He Xiao
collection DOAJ
description Background: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an unfavorable prognosis and limited treatment options. Nevertheless, no clinically applicable molecular markers have been identified for the progression of ACCs. DNA methylation alterations were found to contribute to the development of ACC in recent decades.Material and Methods: The aims of the current study was to identify the abnormally methylated differentially expressed genes (DEGs) in ACCs, and to elucidate the mechanistic basis for these changes. Analyses were conducted on gene expression and gene methylation profile datasets to identify the aberrantly methylated DEGs. The DAVID software was used to conduct the analyses of functional enrichment on screened genes. Finally, expression was validated, and the relationship between abnormally methylated DEGs and clinical features was determined via the Oncomine database and The Cancer Genome Atlas (TCGA). To further verify the altered expression and methylation status of our identified genes we also validated these changes at the tissue and cellular levels.Results: We screened and identified 92 differentially expressed genes and 802 abnormally methylated genes. Furthermore, seven aberrantly methylated and dysregulated genes were identified and validated, along with a number of functional enriched pathways. Among these seven genes, the expression or methylation status is significantly correlated with different pathological stages and overall rates of survival. In validation, the expression of seven genes were significantly altered and five genes were hypermethylated in ACC.Conclusions: Our study identified abnormally methylated DEGs and potentially affected pathways in ACCs, from which we could begin to understand the basic molecular mechanisms of these alterations. Moreover, these abnormally methylated genes might serve as therapeutic targets and biomarkers to allow ACC patients to be more precisely diagnosed and effectively treated.
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spelling doaj.art-b61233f3ccbb4f7b8decac5d60dec96b2022-12-22T02:37:52ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922019-07-011010.3389/fendo.2019.00472432446Identification of Seven Aberrantly Methylated and Expressed Genes in Adrenocortical CarcinomaHe Xiao0Weixiang He1Ping Chen2Deqiang Xu3Guang Zeng4Zhuo Li5Zhuo Li6Zhuo Li7Zhuo Li8Zhuo Li9Mingliu Huang10Xinghuan Wang11Michael E. DiSanto12Xinhua Zhang13Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Urology, Shenzhen Sixth People's Hospital, Shenzhen, ChinaThe Sixth Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, ChinaAffiliated Shenzhen Sixth Hospital of Guangdong Medical University, Shenzhen, ChinaShenzhen Key Laboratory for Endogenous Infection, Shenzhen, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartments of Biomedical Sciences & Surgery of Cooper Medical School of Rowan University, Camden, NJ, United StatesDepartment of Urology, Zhongnan Hospital of Wuhan University, Wuhan, ChinaBackground: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an unfavorable prognosis and limited treatment options. Nevertheless, no clinically applicable molecular markers have been identified for the progression of ACCs. DNA methylation alterations were found to contribute to the development of ACC in recent decades.Material and Methods: The aims of the current study was to identify the abnormally methylated differentially expressed genes (DEGs) in ACCs, and to elucidate the mechanistic basis for these changes. Analyses were conducted on gene expression and gene methylation profile datasets to identify the aberrantly methylated DEGs. The DAVID software was used to conduct the analyses of functional enrichment on screened genes. Finally, expression was validated, and the relationship between abnormally methylated DEGs and clinical features was determined via the Oncomine database and The Cancer Genome Atlas (TCGA). To further verify the altered expression and methylation status of our identified genes we also validated these changes at the tissue and cellular levels.Results: We screened and identified 92 differentially expressed genes and 802 abnormally methylated genes. Furthermore, seven aberrantly methylated and dysregulated genes were identified and validated, along with a number of functional enriched pathways. Among these seven genes, the expression or methylation status is significantly correlated with different pathological stages and overall rates of survival. In validation, the expression of seven genes were significantly altered and five genes were hypermethylated in ACC.Conclusions: Our study identified abnormally methylated DEGs and potentially affected pathways in ACCs, from which we could begin to understand the basic molecular mechanisms of these alterations. Moreover, these abnormally methylated genes might serve as therapeutic targets and biomarkers to allow ACC patients to be more precisely diagnosed and effectively treated.https://www.frontiersin.org/article/10.3389/fendo.2019.00472/fulladrenocortical carcinomabio-informaticsmethylationdifferentially expressed genesbiomarkers
spellingShingle He Xiao
Weixiang He
Ping Chen
Deqiang Xu
Guang Zeng
Zhuo Li
Zhuo Li
Zhuo Li
Zhuo Li
Zhuo Li
Mingliu Huang
Xinghuan Wang
Michael E. DiSanto
Xinhua Zhang
Identification of Seven Aberrantly Methylated and Expressed Genes in Adrenocortical Carcinoma
Frontiers in Endocrinology
adrenocortical carcinoma
bio-informatics
methylation
differentially expressed genes
biomarkers
title Identification of Seven Aberrantly Methylated and Expressed Genes in Adrenocortical Carcinoma
title_full Identification of Seven Aberrantly Methylated and Expressed Genes in Adrenocortical Carcinoma
title_fullStr Identification of Seven Aberrantly Methylated and Expressed Genes in Adrenocortical Carcinoma
title_full_unstemmed Identification of Seven Aberrantly Methylated and Expressed Genes in Adrenocortical Carcinoma
title_short Identification of Seven Aberrantly Methylated and Expressed Genes in Adrenocortical Carcinoma
title_sort identification of seven aberrantly methylated and expressed genes in adrenocortical carcinoma
topic adrenocortical carcinoma
bio-informatics
methylation
differentially expressed genes
biomarkers
url https://www.frontiersin.org/article/10.3389/fendo.2019.00472/full
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