Impact of Protein Phosphatase Expressions on the Prognosis of Hepatocellular Carcinoma Patients

Abstract

The study was conducted to unveil the significance of protein phosphatases in the prognosis of hepatocellular carcinoma (HCC) patients and its related molecular biological attributes as well as to discover novel potential biomarkers for therapeutic significance and diagnostic purposes that may benefit clinical practice. Analyzing a data set from 159 HCC patients using high-throughput phosphoproteomics, we examined the dysregulated expression of protein phosphatases. Employing bioinformatic and pathway analyses, we explored differentially expressed genes linked to protein phosphatases. A protein−protein interaction network was constructed using the search tool for the retrieval of interacting genes/proteins database. We quantified a total of 11,547 phosphorylation sites associated with 4043 phosphoproteins from HCC patients. Within this data set, we identified 105 identified phosphorylation sites associated with protein phosphatases; 28 genes were upregulated and 3 were downregulated in HCC. Enriched pathways using Gene Set Enrichment Analysis encompassed oocyte meiosis, proteoglycans in cancer, the oxytocin signaling pathway, the cGMP-PKG signaling pathway, the vascular smooth muscle, and the cAMP signaling pathway. The Kyoto encyclopedia of genes and genomes (KEGG) analysis highlighted pathways like mitogen-activated protein kinase, AMPK, and PI3K-Akt, indicating potential involvement in HCC progression. Notably, the PPI network identified hub genes, emphasizing their interconnections and potential roles in HCC. In our study, we found significantly upregulated levels of CDC25C, PPP1R13L, and PPP1CA, which emerge as promising avenues. This significant expression could serve as potent diagnostic and prognostic markers to enhance the effectiveness of HCC cancer treatment, offering efficiency and accuracy in patient assessment. The findings regarding protein phosphatases reveal their elevated expression in HCC, correlating with unfavorable prognosis. Moreover, the outcomes of gene ontology and KEGG pathway analyses suggest that protein phosphatases may influence liver cancer by engaging diverse targets and pathways, ultimately fostering the progression of HCC. These results underscore the substantial potential of protein phosphatases as key contributors to HCC's development and advancement. This insight holds promise for identifying therapeutic targets and charting research avenues to enhance the comprehension of the intricate molecular mechanisms underpinning HCC.