title: Decreased expression and prognostic role of mitogen-activated protein kinase phosphatase 4 in hepatocellular carcinoma.
abstract: OBJECTIVE
  This study aimed to investigate the potential role and prognostic significance of mitogen-activated protein kinase phosphatase 4 (MKP-4) in the pathology of hepatocellular carcinoma (HCC).
  
  
  METHODS
  Western blot analysis and quantitative real-time polymerase chain reaction were performed to detect MKP-4 expression in HCC tissues, pericarcinomatous liver (PCL) tissues, and proliferating HCC cells. The detailed role of MKP-4 was further explored by MKP-4 downregulation in HepG2 cells using small interfering RNA (siRNA). Specimens of 134 HCC patients who had undergone hepatic resection were immunohistochemically evaluated for MKP-4 expression.
  
  
  RESULTS
  MKP-4 protein and mRNA levels were significantly lower in HCC tissues than in PCL tissues. In vitro, its expression was gradually reduced following release of HepG2 cells from serum starvation. The cell counting kit-8 assay and Annexin-V-Fluos staining indicated that MKP-4 knockdown by siRNA in HCC cells enhanced cell survival and inhibited apoptosis. Univariate and multivariate analyses revealed that MKP-4 was a significant predictor for overall survival (OS) and time to recurrence (TTR). High MKP-4 expression was well correlated with prognosis independent of Edmondson grade and microvascular invasion (P < 0.001).
  
  
  CONCLUSIONS
  MKP-4 expression was downregulated in HCC tissues and proliferating HCC cells and correlated with OS and TTR, which suggested that MKP-4 is a candidate prognostic marker for HCC.
authors: Department of Gastroenterology, Affiliated Hospital of Nantong University, 20# Xisi Road, Nantong, 226001, Jiangsu, China.
authors: Jinxia
authors: J
authors: Liu
authors: Wenkai
authors: W
authors: Ni
authors: Mingbing
authors: M
authors: Xiao
authors: Feng
authors: F
authors: Jiang
authors: Runzhou
authors: R
authors: Ni
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000096:biosynthesis*; D011379:Prognosis
chemical_list: D054639:Mitogen-Activated Protein Kinase Phosphatases