PCNT is a prognostic biomarker correlated with tumor immune microenvironment in hepatocellular carcinoma and promotes tumor progression by inhibiting cell cycle arrest

Abstract

Pericentrin (PCNT), a core pericentriolar material protein during mitosis, is involved in tumorigenesis and development in various cancers. However, its role in hepatocellular carcinoma (HCC) remains unclear. Based on public databases and a cohort with 174 HCC patients, we found that PCNT mRNA and protein expression were elevated in HCC tissues and correlated with unfavorable clinicopathological characteristics and prognosis. In vitro experiments demonstrated that knockdown PCNT expression inhibited the cell viability, migration, and invasion capacity of HCC cells. Multivariate regression analysis suggested that a high PCNT level was an independent risk factor for poor prognosis. In addition, mutation analysis suggested that PCNT was positively correlated to TMB and MSI but negatively correlated to tumor purity. Moreover, PCNT was significantly negatively correlated with ESTIMATE, immune, and Stromal scores in HCC patients. The PCNT expression level was correlated with immune cell infiltration and immune checkpoint-related gene expression in the tumor microenvironment. The single-cell sequencing analysis suggested that higher PCNT expression level was detected in the malignant cells and immune cells (dendritic cells, monocytes, and macrophages cells) in HCC tissues. Enrichment analysis and functional experiments revealed PCNT promoted tumor progression by inhibiting cell cycle arrest. In conclusion, our studies suggested that PCNT can be a potential prognostic indicator correlated with tumor immune microenvironment, suggesting that PCNT can serve as a novel therapeutic target for HCC.