RHBDF2 is correlated with immune infiltrates in hepatocellular carcinoma and may have potential as a biomarker.

Immune checkpoint inhibitors have been approved for the treatment of advanced hepatocellular carcinoma (HCC). However, immunotherapy requires the identification of suitable biomarkers to guide treatment. The gene for rhomboid 5 homolog 2 (IRHom2), which encodes the rhombus protease iRhom2, activates the MAP3K7-dependent pathway and promotes hepatic steatosis. Thus, we hypothesized an involvement of this gene in HCC. We report that RHBDF2 expression is dramatically upregulated in HCC. RHBDF2 upregulation is associated with tumor stage, lymph node metastasis, tumor protein P53 mutation, and worse prognoses in HCC patients. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analysis enrichment analysis indicated that RHBDF2 was involved in immune signal pathways. Moreover, RHBDF2 expression was positively related not only to immune infiltration, but also to immune cell markers. Examination of several types of HCC infiltrated by immune cells revealed that the group with high expression of RHBDF2 showed the worst outcomes. Therefore, RHBDF2 may have potential as a novel biomarker for predicting prognosis and is related to immune infiltrates in HCC.