The Clinical Significance Of Human Dicarbonyl/L-xylulose Reductase In Hepatocellular Carcinoma

Introduction:Hepatic carcinoma, the fifth morbidity and third mortality, is one of commonly malignant neoplasms. So far there is 55 percent number of incident number, including over 90 percent number of HCC in our country. World Health Organization (WHO) indicates that, about two-fifths of 12 million people diagnosed carcinoma can be prevented. Therefore, exploration in and identification with the related gene of hepatic carcinoma, studying deeply on its biologic functions, will contribute to disclosing the pathogenic mechanism and benefit for clinic diagnosis and treatment. However, DCXR has many roles in different aspects, like acting as carbonyl reductase and preforming non-catalytic functions, interacting with other proteins. Meanwhile, the character about prominent down-regulation in lots of HCCs’ patients, shows that it may serve as effectively biological marker. We provide further research on the mechanism of expression or differential expression in HCC, and discuss the possibility of role in marker.Methods:The differential genes from a patient who has multiple tumors was screened by RT-PCR, and was evaluated by GO analysis in the part of function. Then, collecting the informations of study are from internet. Based on the level of mRNA, DCXR also is examined by qPCR. Meanwhile, WB and IHC detect the expression in the aspect of protein, and IHC analyses the localization in cells and tissues. Using the statistical analysis, we know the meaning if DCXR acts as tumor marker. Otherwise, we study on the role in the development of hepatic cancer through the cell proliferation assay and the key genes in EMT.Results:In our past RT-PCR data, we selected differential genes from a patient who has multiple tumors, and down-regulating DCXR from them was more than 4 folds in tumor tissue compared to non-tumor tissue. In addition, when we utilize Gene Ontology (GO) analysis and find DCXR is a metabolic enzyme in Pentose and glucuronate interconversions pathway. By Immunological histological Chemistry (IHC) analyzing 63 samples which has been diagnosed HCC, the level of DCXR expression in cancer tissues is lower than adjacent non-cancerous tissues, and both PCR and WB also display the same result.In other word, the two aspects of nucleic acid (NA) and protein are consistent meaning. We discuss other 36 hepatic samples, including 1 Hepatic Hemangioma Cavernosum (HA), 14Intrahepatic cholangiocarcinoma(CCC), 6 cholangioadenoma (CA),1 gallbladder cancer (GBC),4 cholangiocarcinoma and 10 liver metastasis (LM)(2 LMGC,1 LMIC,6 LMCC,1LMRC), also discover that the DCXR expression in all of tumor tissues is obviously lower than non-tumor tissue. Analyzing clinical information of the collected tissue samples suggests that DCXR expression in cancer is correlation with the total bilirubin (tbile) of blood (p<0.05), and IHC previously shows that DCXR expressed commonly in epithelial cell is higher expression in non-tumor tissues. We suppose DCXR can act as biological marker and analyze the sensibility and specificity from the collected samples, and conclude that the sensibility is 67.1 percent, specificity 72.4 percent and the value of ROC (Receiver Operating Curve) 0.763. Moreover, total bilirubin between HCC and other hepatic tumors, there are normal and abnormal condition, but DCXR expression in HCC which total bilirubin exceeds in is more evident. We exert the gene-knockout/overexpression technology and the cell proliferation assay, therefore prove that DCXR inhibits cell proliferation. We already know that the relevant genes of Epithelial Mesenchymal Transition (EMT), such as fibronectin, vimentin, snail and slug, are apparently changed. Those results explain DCXR makes a negative regulation in the development of hepatic neoplasms. However, there is not predictive consequence when using 5-Aza-dC (a drug of demethylation) changes the inhibiting regulation of DCXR.Conclusion:Our research suggests that, DCXR is prominent down-regulation in hepatic carcinoma and locates in epithelial cells. Both sensibility and specificity explain further it may play tumor maker in human, and it is no relevant with other factors associated with prognosis except for the index of total bilirubin. In addition, it can promote cell proliferation, and plays negative regulation by EMT analysis in liver cancer. Finally, those developing results indicate that, the differential expression of DCXR may be acted as tumor marker in hepatic cancers, particularly HCCs.