PRRC2A Promotes Hepatocellular Carcinoma Progression and Associates with Immune Infiltration.

Purpose: Hepatocellular carcinoma (HCC) has high morbidity and poor prognosis due to the propensity of recurrence and metastasis. Emerging studies have confirmed that proline-rich coiled-coil2A (PRRC2A) plays a crucial role in tumorigenesis and immunoregulation. However, its expression status and biological functions in HCC remain poorly documented.

Methods: The presence and prognostic value of PRRC2A were determined by a tissue microarray (TMA) cohort and multiple databases, mainly from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC). Functional enrichment analysis was applied to identify the mechanisms of PRRC2A in HCC. The biological function of PRRC2A in HCC progression in vitro was determined by CCK-8, colony formation, EdU, transwell migration and invasion assays. Moreover, the Estimation of STromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE), single-sample gene set enrichment analysis (ssGSEA), tumor immune dysfunction and exclusion (TIDE) algorithms, immunophenoscore (IPS) and public available immunotherapy cohorts were performed to classify their associations with tumor-infiltrating immune cells and immunotherapy.

Results: PRRC2A was upregulated in HCC at both mRNA and protein levels. High PRRC2A expression was correlated with poor prognosis and could be an independent risk factor. Functional enrichment analysis demonstrated that elevated PRRC2A was significantly correlated with the activation of various oncogenic pathways. Additionally, in vitro experiments confirmed that silencing PRRC2A could suppress the proliferation and metastasis capacities of HCC cells. More importantly, PRRC2A was negatively associated with many anti-tumor immune cells, but positively related to the expression of markers of exhaustive T cells. And HCC patients with high PRRC2A were more likely to be nonresponsive to immunotherapy.

Conclusion: This study explored the predictive value and biological roles of PRRC2A in HCC progression and indicated that it might be a potential biomarker for HCC patients and a predictor for immunotherapy.