High Expression of PIGC Predicts Unfavorable Survival in Hepatocellular Carcinoma

Purpose: The effects of phosphatidylinositol glycan anchor biosynthesis, class C (PIGC), in the progression of liver cancer are unknown. In this study, we attempted to clarify the clinical significance and mechanism of PIGC in hepatocellular carcinoma (HCC). Patients and Methods: To explore the expression profiles, DNA methylation, mutation status, clinical relevance, and prognostic value of PIGC in patients with HCC, a series of bioinformatic databases and websites were searched. Moreover, numerous vitro experiments were performed to investigate the mechanism of PIGC in the regulation of cancerous liver cells. Results: Expression of PIGC mRNA and protein was upregulated in cancerous liver specimens compared with normal liver tissues. High expression of PIGC mRNA was related to higher tumor grade, lymphatic metastasis, advanced TNM stage, and TP53 mutation. High expression of PIGC mRNA predicted more unfavorable overall survival (OS) (HR=1.7, P=0.0028) and disease-free survival (DFS) (HR=1.5, P=0.0067) in patients with liver cancer. The mutation rate of PIGC was 10%, and amplification was the most common mutant type. Expression of PIGC mRNA was negatively regulated by its DNA methylation (r=-0.398, P<0.0001). Moreover, silencing of PIGC in HepG2 cell line inhibited the proliferation and migration and led to cell cycle arrest at G0/G1 stage by reducing cyclinD1, CDK2, CDK4, and CDK6 expression, while overexpression of PIGC in Hcclm3 cell line revealed the opposite effect. Conclusion: PIGC is related to aggressive clinical features, and overexpression of PIGC signifies worse survival in patients with HCC. PIGC promotes proliferation and migration of cancerous liver cells through the regulation of the cell cycle.