The Relationship Between Vitamin D & Its Receptor And Hepatocellular Carcinoma Related To Hepatitis B Virus

Objective: Liver cancer is a kind of liver malignant tumor, consisting of primary liver cancer and secondary liver cancer according to liver source, and hepatocellular carcinoma(HCC) accounts for 90% of primary liver cancer.HCC is one of five most common malignant tumor in the world at present,which is the second cancer cause to death. About one million people die of liver cancer each year, about 50% of which happens in China, and it has a high rate of morbidity and mortality. In China, 80% of HCC patients have basic HBV or HCV infection, which has not obvious early clinical symptoms with low diagnosis rate. When made the definite diagnosis, most of the patients are already at the middle and late period and lose the chance of operation, which has high degree of malignancy and tumor biology, the overall 5 year survival rate is low, the prognosis is poor. At present liver cancer is still the main death cause of Chronic viral hepatitis and liver cirrhosis patients. Recent study shows that vitamin D could combine with its receptor to restrain cell proliferation, induce cell death and exert anti-tumor effects. This experiment research on the level of serum vitamin D, liver tissue VDR m RNA and the difference of VDR protein between HCC patients and healthy control group,and the synthesis differences of VDR m RNA, and VDR protein in cancer tissue and para carcinoma tissues, to explore the vitamin D and the development of liver cancer in rats and the possible mechanism of antitumor,through the synthesis of D level of serum vitamin, VDR m RNA liver tissue and VDR protein.Methods: This study collects 32 cases of patient in Hebei Medical University Third Hospital from March 2013 to November 2014, including 20 cases of HCC patients, comparing with 12 cases of healthy people as healthy control group from the Hebei Medical University Third Hospital during thesame period. This study also collect 10 cases of HCC patients who received a liver tissue transplant and 4 cases of normal donor liver tissue. HCC and CHB diagnosis were consistent with the diagnosis standard in "Guide of diagnosis and treatment of liver cancer in China"(2009) and “Prevention and Treatment for Chronic Hepatitis B in China”(2010), jointly established by the Chinese Medical Association Branch of Infectious Diseases and Chinese Society of Hepatology. Detect the serum biochemical indexes of the patients,blood coagulation function and HBV DNA load and detect the VDR m RNA in liver tissue using real-time fluorescent quantitative PCR, the VDR express part in liver tissue by immunohistochemistry, Western Blot detection system liver tissue VDR protein expression, and the serum vitamin D levels by enzyme linked immunoassay. Compare the differences of serum vitamin D level in HCC patients and healthy controls.Results:1 HCC group, healthy control group of demographic and clinical characteristicsThere is comparability of the age and sex of the patients in HCC group and healthy control group. Serum albumin of liver cancer patients(ALB)(31.71±5.08) and prothrombin activity(PTA)(89.77±7.77) are all lower than the(ALB)(36.91±4.73) 、 PTA(107.58±6.89) of the healthy control group.Alanine aminotransferase(ALT)(62.95±40.20), aspartate aminotransferase(AST)(39.90±21.51) and direct bilirubin(DBIL)(4.29±1.87) are all higher than the ALT(6.28±3.26)、AST(16.26±4.41)and DBIL(3.55±1.26)of the healthy control group. While there is no obvious difference of total bilirubin(TBIL)(14.81±4.29) and TBIL(12.11±1.87) of healthy control group. The results are all statistically significant(P<0.01).2 The level of serum VD for the HCC patients There was an decrease of VD levels in HBV-related HCC patients. The VD levels were significantly different between HCC(40.59±9.39 ng/ml) and normal groups(93.42±24.13 ng/ml),(P<0.01)and the HBV-related HCC patients had the lower VD level.3 The expression of VDR protein in the HCC and normal patient liversThe detection of VDR by Immunohistochemistry is all expressed in hepatocellular carcinoma tissue, para carcinoma tissue and normal tissue.Vitamin D receptor was mainly expressed in the cytoplasm, and there is not expression in the nucleus in hepatocellular carcinoma tissue, para carcinoma tissue and normal tissue. Detect the expression of VDR in hepatocellular carcinoma tissues, para carcinoma tissue and normal tissue using RT-PCR method. The results show that: VDR m RNA(2.77±0.30) is higher in cancer tissue, with statistical significance. It is also significantly higher than that in adjacent to cancer tissue(1.62 ± 0.21) and normal liver tissues(1.57 ± 0.19),with statistical significance(P<0.01). Western Blot showed that the expression of VDR protein in hepatocellular carcinoma(1.15±0.57) was significantly higher than that in adjacent to cancer tissue(1.02±0.25) and normal tissue(0.37±0.11).Conclusions:1 The serum vitamin D levels of patients with liver cancer are significantly higher than that of the normal control group, which shows that vitamin D is closely related to the HCC.2 Vitamin D receptor was mainly expressed in the cytoplasm, and there is not expression in the nucleus in hepatocellular carcinoma tissue, para carcinoma tissue and normal tissue.3 The expression of vitamin D receptor in hepatocellular carcinoma is higher than its expression in the normal tissues of liver, which indicates that vitamin D receptor is relevant to the occurrence and development liver cancer.