Potential Role and Clinical Value of PPP2CA in Hepatocellular Carcinoma

Background and Aims: Protein phosphatase 2A (PP2A) is associated with many cancers. This study aimed to clarify whether PPP2CA, which encodes the alpha isoform of the catalytic subunit of PP2A, plays a role in hepatocellular carcinoma (HCC) and to identify the potential underlying molecular pathways. Methods: Based on bioinformatics, public databases and our in-house RNA-Seq database, we analyzed the clinical value and molecular mechanism of PPP2CA in HCC. Results: Data were analyzed from 2,545 patients with HCC and 1,993 controls without HCC indexed in The Cancer Genome Atlas database, the Gene Expres-sion Omnibus database and our in-house RNA-Seq data -base. PPP2CA expression was significantly higher in HCC tissue than in non-cancerous tissues (standardized mean difference: 0.69, 95% confidence interval [CI]: 0.50- 0.89). PPP2CA expression was able to differentiate HCC from non-HCC, with an area under the summary receiv-er operator characteristic curve of 0.79 (95% CI: 0.75- 0.83). Immunohistochemistry of tissue sections confirmed that PPP2CA protein was up-regulated in HCC tissues. High PPP2CA expression in HCC patients was associated with shorter overall, progression-free and disease-free survival. Potential molecular pathways through which PP-P2CA may be involved in HCC were determined using miR-Walk 2.0 as well as analysis of Gene Ontology categories, Kyoto Encyclopedia of Genes and Genomes pathways, and protein-protein interaction networks. Conclusions: PP-P2CA is up-regulated in HCC and higher expression cor-relates with worse prognosis. PPP2CA shows potential as a diagnostic marker for HCC. Future studies should ex-amine whether PPP2CA contributes to HCC through the candidate microRNAs, pathways and hub genes identified in this study.