Shared Genes and Molecular Mechanisms between Nonalcoholic Fatty Liver Disease and Hepatocellular Carcinoma Established by WGCNA Analysis

Juan He; Xin Zhang; Xi Chen; Zongyao Xu; Xiaoqi Chen; Jiangyan Xu

doi:10.1055/s-0043-1768957

Shared Genes and Molecular Mechanisms between Nonalcoholic Fatty Liver Disease and Hepatocellular Carcinoma Established by WGCNA Analysis

Glob Med Genet. 2023 Jul 10;10(3):144-158. doi: 10.1055/s-0043-1768957. eCollection 2023 Sep.

Authors

Juan He¹, Xin Zhang², Xi Chen², Zongyao Xu², Xiaoqi Chen², Jiangyan Xu¹

Affiliations

¹ Traditional Chinese Medicine (ZHONG JING) School, Henan University of Chinese Medicine, Zhengzhou, Henan, People's Republic of China.
² First School of Clinical Medicine, Henan University of Chinese Medicine, Zhengzhou, Henan, People's Republic of China.

Abstract

Background Hepatocellular carcinoma (HCC) is one of the leading causes of death from cancer worldwide. The histopathological features, risk factors, and prognosis of HCC caused by nonalcoholic fatty liver disease (NAFLD) appear to be significantly different from those of HCC caused by other etiologies of liver disease. Objective This article explores the shared gene and molecular mechanism between NAFLD and HCC through bioinformatics technologies such as weighted gene co-expression network analysis (WGCNA), so as to provide a reference for comprehensive understanding and treatment of HCC caused by NAFLD. Methods NAFLD complementary deoxyribonucleic acid microarrays (GSE185051) from the Gene Expression Omnibus database and HCC ribonucleic acid (RNA)-sequencing data (RNA-seq data) from The Cancer Genome Atlas database were used to analyze the differentially expressed genes (DEGs) between NAFLD and HCC. Then, the clinical traits and DEGs in the two disease data sets were analyzed by WGCNA to obtain W-DEGs, and cross-W-DEGs were obtained by their intersection. We performed subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) enrichment analyses of the cross-W-DEGs and established protein-protein interaction networks. Then, we identified the hub genes in them by Cytoscape and screened out the final candidate genes. Finally, we validated candidate genes by gene expression, survival, and immunohistochemical analyses. Results The GO analysis of 79 cross-W-DEGs showed they were related mainly to RNA polymerase II (RNAP II) and its upstream transcription factors. KEGG analysis revealed that they were enriched predominantly in inflammation-related pathways (tumor necrosis factor and interleukin-17). Four candidate genes (JUNB, DUSP1, NR4A1, and FOSB) were finally screened out from the cross-W-DEGs. Conclusion JUNB, DUSP1, NR4A1, and FOSB inhibit NAFLD and HCC development and progression. Thus, they can serve as potential useful biomarkers for predicting and treating NAFLD progression to HCC.

Keywords: WGCNA; bioinformatics; genes; hepatocellular carcinoma; nonalcoholic fatty liver disease.

The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).

Grants and funding

Funding This research was funded by Henan Province Characteristic Backbone Discipline TCM Discipline Construction Project (STG-ZYXKY-2020019) and Henan Province Characteristic Backbone Discipline Chinese Medicine Second Batch Discipline Construction Project (STG-ZYX03-202126).