<p>Expression Pattern and Prognostic Utility of PME-1 in Patients with Hepatocellular Carcinoma</p>

Abstract

Purpose: Hepatocellular carcinoma (HCC) remains one of the most common malignancies. While there is lack of markers capable of predicting which patients are at risk of aggressive course of the disease. Although a few protein phosphatase methyl-esterase-1 (PME-1) tumor-promoting mechanisms have been reported, the role of PME-1 in cancer including HCC occurrence and progression remains to be elucidated. The aim of this study was to explore the expression pattern and relationship between PME-1 with the pathological parameters in patients with HCC. Methods: PME-1 expression was assessed from HCC tissue chips via immunohistochemistry. Chi-square test was used to identify the association between PME-1 staining and clinicopathological variables of HCC patients. Kaplan-Meier analysis and Cox regression analysis were performed to draw survival curves and verify the independent prognostic factors of HCC patients, respectively. Results: We found that PME-1 expression was significantly higher in HCC tumor tissues compared with non-tumor tissues (P < 0.001). Furthermore, high expression level of PME-1 was significantly associated with differentiation (P = 0.047), tumor number (P = 0.001), intrahepatic or extrahepatic metastasis (P = 0.018), and recurrence (P = 0.001). Kaplan-Meier analysis revealed that high expression level of PME-1 was associated with shorter survival (P < 0.001). Univariate analysis with Log-rank test revealed that PME-1 expression status was significantly correlated with overall survival (P < 0.001). Furthermore, multivariate models with Cox proportional hazards analysis showed that high expression of PME-1 was a statistically independent predictive factor of poor prognosis in HCC patients (hazard ratio, 3.429; 95% confidence interval, 1.369-8.589; P = 0.009). Conclusion: In conclusion, these findings indicated that PME-1 expression was associated with aggressive pathological features and worse oncological outcomes, suggesting its potential therapeutic value for patients with HCC.

Biased holoenzyme assembly of protein phosphatase 2A (PP2A): From cancer to small molecules

“…The levels of carboxymethylated PP2A has been correlated with cancer progression and both progression free and overall survival in patient cohorts. Decreased PP2A carboxymethylation has been associated with increased cancer progression possibly as a result of loss of specific B subunit binding to the carboxymethylated PP2A A/C dimer ( 21 , 92 ). Additionally, modulation of PP2A carboxymethylation has been studied in the context of cancer therapeutic response, where overexpression of PME-1 was found to drive kinase inhibitor resistance in glioma cells and knockdown of PME-1 increased sensitivity to epidermal growth factor receptor (EGFR) and Polo-Like Kinase 1 (PLK1) inhibitors in lung adenocarcinoma cells ( 93 ).…”