Protein Regulator of Cytokinesis 1 (PRC1) Upregulation Promotes Immune Suppression in Liver Hepatocellular Carcinoma.

Abstract

Liver hepatocellular carcinoma (LIHC) is a malignant cancer with widespread prevalence. The suppressive immune environment causes largely refractory to current treatment. The protein regulator of cytokinesis 1 (PRC1) is an essential gene for cytokinesis and is involved in cancer pathogenesis. However, the functions of PRC1 have been barely clarified, especially in LIHC. Here, we investigated the expression, prognostic value, and functions of PRC1 in LIHC. Pan-cancer analysis revealed the overexpression of PRC1 in the Cancer Genome Atlas (TCGA) database. Four LIHC datasets from the Gene Expression Omnibus (GEO) database confirmed the PRC1 overexpression in LIHC. The mRNA and protein levels of PRC1 in LIHC cells were higher than in normal liver cells. The overexpression of PRC1 predicted progressed clinical stage and poor prognosis of LIHC. We further investigated the functions of PRC1 by performing the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and Gene Set Enrichment Analysis (GSEA) of its coexpressing genes. High PRC1 expression was associated with increased genome instability of LIHC. Moreover, PRC1 was positively correlated with the infiltration of suppressive immune cells like T regulatory cells (Tregs) and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and was negatively correlated with the effector immune cells' infiltration, including B cells and CD8+ T cells. In addition, PRC1 was positively correlated with the expression of tumor immune checkpoint molecules. Taken together, PRC1 overexpression contributes to the genome instability and the suppressive immune microenvironment of LIHC. Thus, PRC1 has the potential to be a prognostic marker and therapeutic target of LIHC.