PRRC2A Promotes Hepatocellular Carcinoma Progression and Associates with Immune Infiltration

Xin Liu; Yize Zhang; Zenghan Wang; Liwen Liu; Guizhen Zhang; Jianhao Li; Zhigang Ren; Zihui Dong; Zujiang Yu

doi:10.2147/JHC.S337111

PRRC2A Promotes Hepatocellular Carcinoma Progression and Associates with Immune Infiltration

J Hepatocell Carcinoma. 2021 Dec 1:8:1495-1511. doi: 10.2147/JHC.S337111. eCollection 2021.

Authors

Xin Liu^#^{1

2

3}, Yize Zhang^#^{2

3}, Zenghan Wang^{1

2

3}, Liwen Liu^{1

2

3}, Guizhen Zhang^{1

2

3}, Jianhao Li^{1

2

3}, Zhigang Ren^{1

2

3}, Zihui Dong^{2

3}, Zujiang Yu^{1

2

3}

Affiliations

¹ Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China.
² Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China.
³ Gene Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China.

^# Contributed equally.

Abstract

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.

Keywords: PRRC2A; hepatocellular carcinoma; immune infiltration; immunotherapy; prognosis.

Grants and funding

This study was supported by National Natural Science Foundation of China (82070643, and U1904164), the China Postdoctoral Science Foundation (2020T130609 and 2020T130109ZX), and Key Scientific Research Projects of Higher Education Institutions in Henan Province (20A320056).