The Expression Of HTA In Hepatocellular Carcinoma And Relevant Research On Expression Between HTA And ADAM9、ADAM17

Background and PurposeHepatocellular carcinoma(HCC) is a kind of cancer that with high incidence, high malignancy and poor prognosis, when the patients has been diagnosed, they are the group of advanced HCC, which has poor effectiveness of therapeutic treatments. Therefore, early diagnosis and treatment of HCC and its recurrence are important to improve the survival rate and the effect of prognosis. The key to early diagnosis is looking for high sensitivity and high specificity of HCC markers.HTA is a new tumor-related gene screened with bioinformatics method and cloned from hepatoma cell lines by the laboratory Dr. Liu Yan. Early results suggested that it is associated with the incidence of HCC, and it may be a potential diagnostic marker for HCC. However, previous studies focused on functionary exploration of HTA, while the studies of expression in various tissues and organs are limited. For the HTA’s expression and its links with clinical pathology research in HCC tissues, corresponding adjacent tissues and normal liver tissues are also undeveloped. Therefore, this study intends to detect HTA’s potential as HCC tumor markers by immunohistochemical, analyze expression and clinicopathological correlation of HTA in HCC. Combined with the results of previous microarray, we design to analyze the correlation expression between HTA and its related difference gene ADAMs, and lay the foundation for improving the early diagnosis rate and prognosis for HCC patients. Methods13kinds of tumor tissue sections were collected, and we detected the expression of HTA in a variety of tumors by immunohistochemistry, moreover, assessed the potential of HTA as a tumor marker for HCC. Hepatocellular carcinoma and corresponding adjacent PL samples from32HCC patients and NL samples from12hepatic hemangioma patients (controls) were collected in the operating room. Correlation between HTA expression and clinicopathologic features were detected by mRNA level and protein level. According to results of gene chip, the correlation between HTA and ADAM9, ADAM17were evaluated using Q-PCR, western blotting and immunohistochemistry in different cell lines and tissues.Results1. By immunohistochemistry, HTA protein was expressed in more than60%of the HCC tissues and moderately expressed in few tumors such as lung cancer(10.87%), gastric cancer(20.00%), colon cancer(35.48%), rectal cancer(14.29%), cervical cancer(23.08%), but not found in esophagus cancer, breast cancer, bladder cancer, kidney cancer, nasopharynx cancer.2. By Q-PCR, HTA was expressed at significantly higher levels in HCC than the corresponding adjacent paracarcinomatous liver(PCL) tissues and normal liver(NL) tissues at the mRNA level(P<0.05).3. By immunohistochemistry, HTA was expressed at significantly higher levels in HCC than the corresponding adjacent paracarcinomatous liver(PCL) tissues and normal liver(NL) tissues at the protein level. The subcellular location of positive staining was predominantly in the cytoplasm.4. Expression of HTA protein was closely related with intrahepatic metastasis of tumors(P<0.05) by χ2analysis. Expression of HTA mRNA was closely related with differentiation and intrahepatic metastasis of tumors by t-test.5. The expression of HTA was positively related with ADAM9, ADAM17in different cell lines and tissues by Q-PCR, western blotting and immunohistochemistry.Conclusion1. HTA expressed highly in HCC, and with low expression or no expression in other tumor tissues.2. The expression of HTA was closely related with intrahepatic metastasis of tumors, but there was no significant correlation between HTA expression and patient gender, age, differentiation, tumor size, ect.3. There is a positive correlation between HTA and tumor metastasis factors ADAM9, ADAM17.