RASGRF2 as a potential pathogenic gene mediating the progression of alcoholic hepatitis to alcohol-related cirrhosis and hepatocellular carcinoma.

Abstract

Background and aims: Alcoholic hepatitis (AH) and hepatocellular carcinoma (HCC) are common liver diseases. Chronic inflammation caused by AH can progress to alcoholic cirrhosis (AC) and eventually HCC.

Methods: This study sought to ascertain potential shared genes between AH and HCC through the utilization of multiple transcriptome databases. Employing an immune infiltration analysis, and calculating the correlation between shared genes and immune infiltration results, in conjunction with independent bulk transcriptome validation sets, led to the identification of core shared genes. Subsequently, single-cell transcriptome data, clinical sample immunohistochemistry experiments, and overexpressed core shared genes in HepG2 cells were employed to validate the core shared genes of AH and HCC.

Results: Through the bulk transcriptome discovery sets of AH and HCC, 206 potential shared genes were identified. After screening with two machine learning algorithms, five shared genes remained. Combining the results of the immune infiltration and bulk transcriptome results from an independent validation cohort, the core shared gene was determined to be RASGRF2. Single-cell data further demonstrated that RASGRF2 and its downstream genes were highly expressed in AH, AC, and HCC tissues. Spatial transcriptome data indicated that RASGRF2 was highly expressed in HCC tumor tissues. Compared with the paracancerous tissues, the RASGRF2 gene was significantly overexpressed in HCC tissues. Overexpression of RASGRF2 in HepG2 cells resulted in significantly enhanced migration, invasion, and proliferation abilities.

Conclusion: RASGRF2 serve as a pathogenic gene that mediates the progression of AH to AC and potentially to HCC.