Decreased expression and prognostic role of mitogen-activated protein kinase phosphatase 4 in hepatocellular carcinoma.

Abstract

PURPOSE:

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: Jinxia Liu, Wenkai Ni, Mingbing Xiao, Feng Jiang, Runzhou Ni
• Journal: Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract (J Gastrointest Surg) Vol. 17 Issue 4 Pg. 756-65 (Apr 2013) ISSN: 1873-4626 [Electronic] United States
• PMID: 23325341 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Mitogen-Activated Protein Kinase Phosphatases

Topics

• Adult
• Aged
• Carcinoma, Hepatocellular (enzymology)
• Cells, Cultured
• Female
• Gene Expression
• Humans
• Liver Neoplasms (enzymology)
• Male
• Middle Aged
• Mitogen-Activated Protein Kinase Phosphatases (biosynthesis)
• Prognosis