The Expression Of PPM1D In Hepatocellular Carcinoma And The Relationship Between Clinical Pathological Features

Background:Hepatocellular carcinoma (HCC) is the fifth most common cancer, and the third leading cause of cancer-related death, worldwide.Early dignosis is very difficult Because it’s lack of specific clinical symptoms,the prognosis of HCC patients remain poor. Surgical resection of the tumor offers a chance for cure, but does not achieve optimal long-term survival, mainly due to recurrence and metastasis. It is important to find the prognostic predictors for HCC. Much effort has made to identify the molecular markers correlating with the survival of HCC patients. But there is still lack of specific prognostic indicators. Protein phosphatase magnesium-dependent1δ(PPM1D) is an oncogene, overexpressed in many solid tumors, including ovarian cancer and breast cancer. Presently there are no studies about the expression change of PPM1D in Hepatocellular carcinoma and the relationship of it’s clinicopathologic feature.Objective:1. The study examined the PPM1D expression in Hepatocellular Carcinoma, examine the correlation of carcinogenesis and PPM1D expression.2. examine the prognostic value of PPM1D mRNA in human hepatocellular carcinoma (HCC) and the correlation with clinical pathologic factors(tumor size,AFP level, TNM stage recurrence incidence etc.).Methods:1. Immunohistochemistry assay was used to verify the expression of ppmld protein in the HCC and non-cancerous liver tissues.2. PPM ID mRNA expression was determined by real-time quantitative reverse transcriptase-polymerase chain reaction. HCC patients were grouped according to PPM1D mRNA expression with the average PPM1D mRNA level in non-cancerous liver tissue samples as the cut-off. Correlations between clinicopathologic variables(tumor size,AFP level, TNM stage,recurrence incidence etc.) and PPM1D mRNA expression were analyzed.Findings:1.in the86HCC tissues and paired noncancerous liver tissues, Immunohistochemistry revealed that PPM1D expression in83patients (96.5%)was overlapping with mRNA expression. PPM1D expression was higher in HCC tissues than in non-cancerous liver tissues.The difference was statistically significant (p<0.01).2.In the86tumor and adjacent normal liver tissue specimens, the expression of PPM ID mRNA was positive. PPM1D mRNA was significantly higher in HCC than in the paired non-cancerous tissue (p<0.01). This was confirmed by ppmld staining.56patients were classified as high expression group and the other30patients were categorized as low expression group. There were significant differences between the two groups in term of alphafetoprotein (AFP) level (p<0.01), tumor size (p<0.01), TNM stage (p<0.01), recurrence incidence (p<0.01) and family history of liver cancer (p<0.01). The current study failed to find significant differences between the two groups in the following clinical characteristics:age, gender, portal vein invasion, lymphnode metastasis, hepatitis B virus (HBV) infection and alcohol intake. Survival time of high expression group was significantly shorter than that of low expression group (median survival,13months and32months, respectively, p<0.01).Conclusion:1. PPM1D expression was higher in HCC tissues than in non-cancerous liver tissues,which is associated with carcinogenesis.2.Up-regulation of PPM1D mRNA was associated with progressive pathological feature in HCC patients. PPM1D mRNA expression in patients with high degree of tumor malignant and invasive are significantly higher than patients with lower expression.3.PPM1D mRNA may serve as a prognostic marker in HCC, PPM1D mRNA expression in patients with high survival significantly lower than patients with lower expression, The prognosis is poorer.