Protein phosphatase magnesium-dependent 1δ is a novel tumor marker and target in
PUBLISHED: 2015-11-27  255 total views, 1 today

Chunxiang Cao1, Zhi Xu2, Haiyan Xia2, Jianmin Bian2, Wenbin Huang2Yixin Zhang3, Song He4, Nikki Lee5

1Department of Oncology, Nanjing First Hospital, Nanjing Medical University, 2Nanjing Medical University, Nanjing First Hospital, 3Department of General Surgery, Nantong Tumor Hospital, 4Department of Pathology, Nantong Tumor Hospital, 5Department of Surgery, The University of Hong Kong

 

Objective:Hepatocellular carcinoma (HCC) is a lethal malignancy worldwide and lacking effective medication. Protein phosphatase magnesium-dependent 1δ (PPM1D) is a potential oncogene and promising prognostic marker in a variety of solid tumors. We aimed to investigate the clinical and prognostic value of PPM1D in HCC. Method: Immunohistochemical staining was performed toexamine PPM1D expression in HCC tissue microarrays. The associations between PPM1D expression and individual clinicopathologic variables with overall survival were analyzed by SPSS. We used gain-of-function and loss-of-function experiments to explore the effects of PPM1D in HCC cells, and confirmed the results in tumor xenograft mouse model. Result: A retrospective cohort of 81 HCC patients who underwent hepatectomy were enrolled in this study. Our results showed that PPM1D was highly expressed in the majority of HCC cases (approximately 59%) and significantly associated with high serum α-fetoprotein (AFP) level (P=0.044). Kaplan-Meier and Cox regression data indicated that PPM1D overexpression was an independent predictor for HCC-specific overall survival (HR, 2.799; 95% CI, 1.346-5.818, P=0.006). Overexpressing PPM1D could promote cellular viability and invasion, while RNA interference–mediated knockdown of PPM1D could inhibit proliferation, cellular invasion and migration in HCC cell lines. In addition, we found that PPM1D small interfering RNA was able to decrease tumorigenicity of HCC cells in vivo. Conclusion: Our results suggest that PPM1D is a prognostic marker and attractive therapeutic target for this aggressive malignancy.

 

Key Words: PPM1D  hepatocellular carcinoma  prognosis


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