Bioinformatics‐based identification of hepatocellular carcinoma‐associated hub genes and assessment of the restorative effect of tannic acid in rat liver exposed to monosodium glutamate

Abstract

AbstractBackgroundHepatocellular carcinoma (HCC) is the most common type of primary liver cancer, occurring mostly in individuals with chronic liver disease, but biomarkers for therapeutic diagnosis and prognosis are lacking. This study aimed to investigate the possible effect of the common food additive monosodium glutamate (MSG) and tannic acid (TA), a phenolic compound, on the key molecular actors responsible for HCC development.MethodsEight HCC‐related public microarray datasets (GSE84005, GSE14520, GSE25097, GSE57958, GSE22058, GSE84402, GSE54238, and GSE36376) were extracted from the gene expression omnibus (GEO) database and analyzed to identify differentially expressed genes (DEGs). To make sense of the identified biological data and to identify hub genes, protein–protein interaction (PPI) network and enrichment analysis were performed. The mRNA expression profiles of the identified hub genes, expression changes in different stages of HCC, and their prognostic significances in HCC were determined using GEPIA, UALCAN, and Kaplan–Meier Plotter databases, respectively. Finally, mRNA expression changes of identified hub genes in the liver tissues of rats treated with MSG and TA were measured by the quantitative real‐time PCR (qPCR) method.ResultsTwo up‐regulated (AURKA and CCNB2) and two down‐regulated (F9 and CYP2E1) genes were identified between the HCC tumor and adjacent non‐tumor liver tissue samples. qPCR results showed that the mRNA expression of up‐regulated DEGs involved in HCC development increased significantly in rat liver tissues exposed to MSG, while this increase was remarkably suppressed by TA treatment. It was observed that the mRNA expressions of down‐regulated DEGs involved in HCC development decreased markedly in the presence of MSG, while this decrease was alleviated with TA.ConclusionOur results provide new insights into pivotal molecular candidates that should be focused on in future in vivo and in vitro HCC research. Moreover, MSG may play a crucial role in HCC development and progression and TA may be used as a favorable restorative agent in HCC.