The effect of PPP2CA expression on the prognosis of patients with hepatocellular carcinoma and its molecular biological characteristics

Jingchang Liang; Yu Huang; Chenglei Yang; Shen Huang; Jinlong Xie; Xiang Nong; Jianyong Liu; Yumei Zhang; Zhiming Zhang

doi:10.21037/jgo-21-720

The effect of PPP2CA expression on the prognosis of patients with hepatocellular carcinoma and its molecular biological characteristics

J Gastrointest Oncol. 2021 Dec;12(6):3008-3021. doi: 10.21037/jgo-21-720.

Authors

Jingchang Liang^#¹, Yu Huang^#², Chenglei Yang¹, Shen Huang¹, Jinlong Xie¹, Xiang Nong¹, Jianyong Liu¹, Yumei Zhang^#², Zhiming Zhang^#¹

Affiliations

¹ Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China.
² Department of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning, China.

^# Contributed equally.

Abstract

Background: To investigate the role of the PPP2CA gene in the prognosis of patients with hepatocellular carcinoma (HCC) and its molecular biological characteristics.

Methods: We performed comparison of the expression of PPP2CA in HCC and non-HCC tissues of HCC patients who underwent surgery for the first time in the Tumor Hospital of Guangxi Medical University from July 2017 to July 2019, and retrospectively analyzed the relevant clinical data and prognosis. The GSE76427 data set and bioinformatics and public databases were used to compare the expression of PPP2CA between HCC and non-cancer tissues. Gene Ontology (GO) analysis was performed of PPP2CA and its differential genes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. A protein-protein interaction (PPI) network of PPP2CA and its differentially expressed genes (DEGs) was constructed from the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and visualized by Cytoscape software.

Results: The immunohistochemistry (IHC) of tissue sections confirmed that PPP2CA was highly expressed in most HCC tissues; the high expression of PPP2CA was significantly correlated with microvascular invasion (MVI) and portal vein tumor thrombi (P<0.05). Participants in the PPP2CA high expression group had worse overall survival (OS; P=0.04) and recurrence-free survival (RFS; P=0.019). The PPP2CA gene and 71 DEGs were mainly enriched in the nuclear division, organelle fission, nuclear chromosome separation, and chromatid separation process, and KEGG analysis revealed enrichment in drug metabolism-cytochrome metabolism of xenobiotics by P450 and cytochrome P450. Finally, through the PPI network, CCNA2, AURKB, TOP2A, NCAPG, MCM2, CDC20, CCMB2, AURKA, and MGST1 were identified as the top 9 highly connected hub genes.

Conclusions: The PPP2CA gene is highly expressed in HCC tissues. The high expression of PPP2CA is significantly associated with poor prognosis. Through the analysis of DEGs, GO and KEGG pathway analysis, it was found that PPP2CA may act on liver cancer through multiple targets and multiple pathways, and PPP2CA plays a promoting role in HCC.

Keywords: Hepatocellular carcinoma (HCC); PPP2CA; bioinformatics; prognosis.