| Background:Primary liver cancer is one of the most common malignant tumors of the digestive system in our country.The World Health Organization reported date showed that the incidence of primary liver cancer in all tumors located in fifth, the mortality located in third.There are also data reported that primary liver cancer incidence and mortality trend were getting younger gradually. Currently a variety of treatment strategies for primary liver cancer could not significantly prolong survival in patients with liver cancer effectively. In recent years,the tumor immunotherapy achieved rapid development and breakthrough.The development of CAR-T brought a new dawn for the treatment of liver cancer. Some scholars through gene fusion technology prepared glypican-3-specific CAR-T cells.And through the experiments in vivo and vitro confirmed the glypican-3 specificity CAR-T having effective killing potential to the glypican-3 positive expression cells in hepatocellular carcinoma.Objective:Detected the expression of glypican-3 in primary hepatocellular carcinoma(HCC),hepatic duct carcinoma and normal liver tissue by Reverse transcription-polymerase chain reaction(RT-PCR) and organization immunochemical method.Through the comparison and analysis.To investigate glypican-3 expression in human primary liver cancer and its significance in clinical significance as a targeting molecular of CAR-T.Methods:The expression of glypican-3 mRNA and glypican-3 protein were detected by Reverse transcription-polymerase chain reaction(RT-PCR) and organization immunohistochemical chemistry in 72 cases of hepatocellular carcinoma,27 cases of hepatic duct carcinoma and 4 cases of normal liver tissue,the 4 normal liver tissues were removed due to hepatolith as controls.All the cases were collected from March2012 to October 2015 during the First Hospital of Shanxi Medical University, and had been removed by surgery and diagnosed by the pathologists in department of pathology.Through the comparison, analyzed the specific expression of glypican-3 in primary hepatocellular carcinoma,hepatic bile duct carcinoma and normal liver tissue.Results:1.The positive expression rate of glypican-3 mRNA and glypican-3 protein was61/72(84.72%) in hepatocellular carcinoma, while 5/27(18.52%) in hepatic bile duct carcinoma,but the expression in 4 cases of normal liver tissue was negative.2.The expression of glypican-3 mainly located on the cytoplasm and cell membrane of primary liver cancer cells, and the correlation between positive expression rate of glypican-3 and differentiation degree of human hepatocellular carcinoma was closely. In the highly differentiated hepatocellular carcinoma,over-positive expression of glypican-3 protein in 37/49 and weak positive expression of glypican-3 protein in 12/49, the positive expression rates was 100%.In the moderately differentiated carcinoma, the over-positive expression of glypican-3protein in 8/14, weak positive expression of glypican-3 protein in 2/14 and negative expression of glypican-3 protein in 4/14, the positive expression rate was 71.43%.In undifferentiated hepatocellular carcinoma, weak positive expression of glypican-3protein in 2/9 and negative expression of glypican-3 protein in 7/9, the positive expression rate was 22.22%.In 4 cases of normal liver tissue, all the expression ofglypican-3 protein was negative.X2=32.451,P<0.001, the difference was statistically significant.3.Glypican-3 came a little expression in hepatic bile duct carcinoma.Over-positive expression of glypican-3 protein in 2/27 and weak positive expression of glypican-3 protein in 3/27 and negative expression of glypican-3 protein in 22/27 in hepatic duct carcinoma, the positive expression rate was 18.52%(5/27).And it had correlation between positive expression rate of glypican-3 and differentiation degree of human hepatic bile duct carcinoma.Over-positive expression of glypican-3 protein in 2/10 and weak positive expression of glypican-3 protein in 2/10,the positive expression rate was 14.81% in 10 cases of the high differentiation hepatic bile duct carcinoma.In the differentiated hepatocellular carcinoma, the over-positive expression of glypican-3 protein in 0/16, weak positive expression of glypican-3 protein in 1/16 and negative expression of glypican-3 protein in 15/16,the positive expression rate was 3.70%.Weak positive expression of glypican-3 protein in 0/1 and negative expression of glypican-3 protein in 1/1 in undifferentiated hepatocellular carcinoma,the positive expression rate was 0. P=0.045, the difference was statistically significant.And there was no difference between the expression of glypican-3 and patients’ clinicopathological parameters like age,sex,tumor size,clinical staging and HBsAg(P>0.05), the difference was not statistically significant.4.The expression of glypican-3 was widely in hepatocellular carcinoma, the positive expression rate was 84.72%(61/72); and came a little expression in hepatic bile duct carcinoma, the positive expression rate was 18.52%(5/27); and all negative expression in 4 cases of normal liver tissue. X2=44.369,P<0.001, the difference was statistically significant.Conclusion:The over-positive expression of glypican-3 mainly located on the the cytoplasm and cell membrane of human hepatocellular carcinoma, and with high specificity. It could be used for the early diagnosis of primary hepatocellular carcinoma,and couldbe as tumor-specific marker in CAR-T and use in human hepatocellular carcinoma targeted therapy. |
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