Clinical Significance And Application Research Of Protein Sialylation In Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, isthe fifth most common cancer worldwide. The aggressive behaviors of HCC, the pooreffectiveness of therapeutic treatments, and lack of early diagnosis of liver cancer withhigh sensitivity and specificity of markers represent the reasons for the annual incidenceand deaths gradual growth. HCC has been ranked third in cancer-relateddeath.Pathological, laboratory and radiologic imaging all aid in diagnosis but each has itsown limitation. Nevertheless, we do not give up seeking higher sensitivity and specificityof the new non-invasive serum marker.The occurrence and development of HCC is composed of a complex series ofbiological events, is a multi-step process of a multi-molecular cascade participation. Asthe molecules involved in this process are mostly glycoproteins, it is very important tostudy changes in cell surface glycoproteins and sugar chain structure to explaintumorigenesis, development, invasion and metastasis. Sialic acid (SA) is a general termfamily of nine-carbon sugar neuraminic acid and is usually located in glycosylatednon-reducing end of glycoprotein and glycolipid. The sialylation plays a crucial role inmany biological processes. The present study is to assess the clinical significance of sialicacid modification in hepatocellular carcinoma.Part1: The clinical studies of serum sialic acid in hepatobiliary and pancreaticcarcinomaThis study is mainly based on a large sample of serum cases, and investigates thechange of serum sialic acid in patients with normal healthy people, liver cirrhosis, andhepatocellular carcinoma patients. We were detected serum sialic acid levels in themodeling and validation group by enzyme reaction rate method. In the modeling group,106cases of normal control,97cases of liver cirrhosis and223patients with HCC, serumsialic acid in patients with HCC was significantly higher than the normal control andpatients with cirrhosis, also higher the normal control group than cirrhosis group.According to the clinical and pathological data collected over the same period, to grouppatients with hepatocellular carcinoma, We were found along with the deepening of theTNM staging, the level of serum sialic acid elevating, with the size of the tumorincreasing the level of serum sialic acid elevating, Also the level of serum sialic acid inHCC patients associated with portal vein tumor thrombus and vascular thrombosis weresignificantly higher than serum sialic acid in HCC patients with nowhere portal vein tumor thrombus and vascular thrombosis. Do a correlation analysis showed that serumsialic acid and multiple clinical laboratory indicators of patients with HCC showed acorrelation. We assess the diagnostic efficacy of serum sialic acid by ROC curve and findalpha-fetoprotein (AFP) is still the highest diagnostic value in the identification of normalcontrol by comparison with HCC, but in the identification of HCC and cirrhosis, serumsialic acid has higher diagnostic value than AFP. Multiparameters diagnostic models wereconstructed based on AFP and SA, the accuracy and sensitivity of the diagnostic modelcombining AFP and SA were much increased compared with AFP. There are513cases ofnormal control,82patients with cirrhosis and319patients with HCC in the validationgroup. The statistics and results are generally unified with the modeling group.We also examined the change of serum sialic acid in the biliary and pancreaticdiseases and compared47cases of gallbladder carcinoma,71cases ofcholangiocarcinoma and67cases of benign biliary disease (29cases of biliary cyst and38cases of gallstones) with513cases of normal control. The results showed thatgallbladder carcinoma and cholangiocarcinoma group were significantly higher than thenormal group and benign biliary disease group, while no significant difference betweenbenign biliary disease and normal control. In114cases of pancreatic cancer and27casesof pancreatitis results show that serum sialic acid level in pancreatic cancer was alsosignificantly higher than the normal group.Conclusion: Serum sialic acid can be a clinically useful diagnostic tool for livercirrhosis and hepatocellular carcinoma. It also can have a good prospect in assessingprognosis in HCC. In the biliary and pancreatic carcinoma, serum sialic acid is alsoexpected to become a new diagnostic marker.Part2: The significance of protein sialylation in hepatocellular carcinoma tissuesIn this study, lectin blot was used to detect the expression of sialylation in36patients with hepatocellular carcinoma and their corresponding adjacent tissues. Thestudy found that there was a significant difference between cancer and adjacent cancertissues in SNA lectin with α-2,6-connecting, hepatocellular carcinoma was significantlyhigher than the corresponding adjacent liver tissues, and there was no significantdifference between adjacent cancer tissue and cancer in MAL lectin withα-2,3-connected.Conclusion: Different connections of sialylation were significantly differentiallyexpressed in primary hepatocellular carcinoma. It can be better to reveal the relationship between sialylation and HCC in histologically, and provide a basis for further study of therole of sialic acid in primary liver cancer.Part3: The impact of sialyltransferase on the biological function of liver cancer cellsThe mRNA expression of ST3GAL1, ST3GAL4and ST6GAL1in several hepatomacarcinoma cells had been assayed by Real-time PCR and then to build ST3GAL1andST6GAL1overexpression vector. Through transfected sialyltransferase overexpressionvector to induce gene overexpression, we can further elucidate the biological significanceof sialyltransferase in the development and metastasis of tumor.Conclusion: Sialyltransferase ST3GAL1may be involved in proliferation of livercancer cells, sialyltransferase ST6GAL1can promote migration of liver cancer cells.Sialyltransferase has an important biological significance in primary liver cancerprogression and metastasis.In summary, through the study of this subject, we find that sialylation is closelyrelated to the development of HCC; serum sialic acid is a very important clinical value asto the diagnosis and dynamic monitoring of hepatocellular carcinoma, is expected tobecome a new non-invasive diagnosis of liver cancer marker.