AUTHOR=Chen Ting , Zhang Siwen , Zhou Dongmei , Lu Peipei , Mo Xianglai , Tamrakar Rashi , Yang Xi 

TITLE=Screening of co-pathogenic genes of non-alcoholic fatty liver disease and hepatocellular carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.911808

DOI=10.3389/fonc.2022.911808

ISSN=2234-943X

ABSTRACT=Background: Nonalcoholic fatty liver disease (NAFLD) is a risk factor for hepatocellular carcinoma (HCC). our study aimed to discover the coexisting pathogenic genes of NAFLD and HCC.
Methods: We performed a variance analysis with public data for both diseases. At the same time, weighted gene correlation network analysis (WGCNA) was used to find highly correlated gene modules in both diseases. The darkturquoise gene module was found to be highly correlated with both diseases. Based on the prognostic module genes and the differential genes of the two diseases, we constructed diagnostic and prognostic models by logistic regression, univariate Cox regression, and Lasso regression. Public datasets verified the results. Meanwhile, we built a ceRNA network based on the model genes and explored the related pathways and immune correlation involved in the two diseases by using GO, KEGG, and GSEA enrichment analysis. Immunohistochemistry was used to verify the different expression of ABCC5 and TUBG1 among the normal liver, NAFLD and HCC tissues. PA/OA was used to establish high-fat cell models and RT-qPCR was used to verify the mRNA expression of ABCC5 in lipidization cells.
Results:  A total of 26 upregulated genes and 87 downregulated genes were found using limma package identification analysis. According to WGCNA, the darkturquoise gene module was highly correlated with the prognosis of both diseases. The coexisting genes acquired by the two groups were only three central genes, i.e., ABCC5, DHODH and TUBG1. The results indicated that the diagnostic and prognostic models constructed by ABCC5 and TUBG1 genes had high accuracy in both diseases. The results of immunohistochemistry showed that ABCC5 and TUBG1 were significantly overexpression in NAFLD and HCC tissues compared with normal liver tissues. The Oil Red O staining and  triglyceride identified the successful construction of HepG2 and LO2 high-fat models using PA/OA. The results of RT-qPCR showed that lipidization of LO2 and HepG2 increased the mRNA expression of ABCC5.
Conclusions: ABCC5 and TUBG1 may play an important role in the development of NAFLD to HCC. And lipidization could upregulate the mRNA expression of ABCC5 in HCC.