Investigations on the dysregulated genes in high-fat-fed mice infected with Prevotella intermedia and their possible role in the development of hepatocellular carcinoma

Abstract

Introduction: Hepatocellular carcinoma (HCC) is a leading global cancer, often linked to various factors, including viral infections and metabolic disorders. Recent studies suggest that microbial infections, particularly from oral pathogens like Prevotella intermedia (Pi), may elevate the progression of HCC through dysbiosis and chronic inflammation. Aim: In view of this, the study aimed to identify candidate genes in high-fat diet-fed mice infected with Pi and to assess the relevance of these orthologous genes in the development of human HCC. Materials and methods: The GEO dataset, GSE136937, was employed to identify the differentially expressed genes across two datasets viz., regular chow-fed and high-fat diet-fed mice infected with Pi. A comparison was made between normal vs. high-fat diet-fed mice infected with Pi to demonstrate the influence of the microbial factor on the development of metabolic disorders and cancer. The identified DEGs were subjected to protein-protein interaction (PPI) analysis and gene ontology (GO) assessments. Human orthologs were evaluated for gene expression status and survival using the TCGA dataset. Results: The analysis revealed numerous DEGs between infected and uninfected groups. The top 20 DEGs (16 upregulated, 4 downregulated) were further investigated in liver hepatocellular carcinoma patients (TCGA). Notably, genes RMND1 and CYP3A43 displayed similar expression patterns in both mouse and human datasets. High RMND1 expression was associated with poor prognosis, while low CYP3A43 expression indicated a poor survival outcome in HCC patients. Conclusion: Metabolic disorders in conjunction with microbial dysbiosis together could support the malignant phenotype by modifying the expression profiles of key genes involved in carcinogenesis. More intense experimental and in vivo studies are needed to further confirm the association of these candidate genes with HCC.