Screening the key genes of hepatocellular adenoma via microarray analysis of DNA expression and methylation profiles

Liu,Dan; Liu,Pengfei; Cao,Liye; Zhang,Quan; Chen,Yaqing

doi:10.3892/ol.2017.6673

Screening the key genes of hepatocellular adenoma via microarray analysis of DNA expression and methylation profiles

Authors:
- Dan Liu
- Pengfei Liu
- Liye Cao
- Quan Zhang
- Yaqing Chen
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Affiliations: Department of Ultrasonic Imaging, Zhuhai People's Hospital, Zhuhai, Guangdong 519000, P.R. China, Department of Lymphoma, Sino‑US Center of Lymphoma and Leukemia, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China, Department of Ultrasonic Medicine, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, P.R. China, Department of Hepatobiliary Surgery, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, P.R. China, Department of VIP Ward, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, P.R. China
Published online on: July 26, 2017 https://doi.org/10.3892/ol.2017.6673
Pages: 3975-3980
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to identify the biomarkers involved in the development of hepatocellular adenoma (HCA) through integrated analysis of gene expression and methylation microarray. The microarray dataset GSE7473, containing HNF1α‑mutated HCA and their corresponding non‑tumor livers, 5 HNF1α‑mutated HCA and 4 non‑related non‑tumor livers, was downloaded from the Gene Expression Omnibus (GEO) database. The DNA methylation profile GSE43091, consisting of 50 HCA and 4 normal liver tissues, was also downloaded from the GEO database. Differentially expressed genes (DEGs) were identified by the limma package of R. A t‑test was conducted on the differentially methylated sites. Functional enrichment analysis of DEGs was performed through the Database for Annotation, Visualization and Integrated Analysis. The genes corresponding to the differentially methylated sites were obtained by the annotation files of methylation chip platform. A total of 182 DEGs and 3,902 differentially methylated sites were identified in HCA. In addition, 238 enriched GO terms, including organic acid metabolic process and carboxylic acid metabolic process, and 14 KEGG pathways, including chemical carcinogenesis, were identified. Furthermore, 12 DEGs were identified to contain differentially methylated sites, among which, 8 overlapped genes, including pregnancy zone protein and solute carrier family 22 member 1 (SLC22A1), exhibited inverse associations between gene expression levels and DNA methylation levels. The DNA methylation levels may be potential targets of HCA. The present study revealed that the 8 overlapped genes, including annexin A2, chitinase 3‑like 1, fibroblast growth factor receptor 4, mal, T‑cell differentiation protein like, palladin, cytoskeletal associated protein, plasmalemma vesicle associated protein and SLC22A1, may be potential therapeutic targets of HCA.

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