| Cholangiocarcinoma, Klatskin tumor is a kind of malignant tumor that primarilyoriginates from the mucous epithelium of bile duct from the common bile duct locatedabove the ductus cysticus to right and left hepatic duct, accountsing for about58%-75%extrahepatic bile duct carcinoma and its histologic type is mostly adenocarcinoma. Inrecent years, its morbidity is rising but the pathogenesis mechanism, the aetiological agentof the disease and its predisposing factors remains unclear.Beacause of its stealthiness,when the clinical symptoms including mainly jaundice and abdominal pain appear, most ofthem have reached an advanced stage, so early diagnosis is difficult and crucial. Becausethe extrahepatic bile duct carcinoma located in special anatomical location and itsbiological characteristics of invading its surrounding tissue, blood vessels and nerves, therate of radical surgical resection is very low, its prognosis is poor, postoperativerecurrence rate is high and its mortality also is increasing year by year. Now the diagnosisof the bile duct carcinoma is mainly imaging findings including B ultrasound, CT, MRCPand PTCD et al. Although they are accurate in diagnosing the advancedcholangiocarcinoma, for the early stage ones, its diagnostic accuracy is very dismal,so thesurvival time of patient do not have obvious increase. It is generally considered that CEA,CA242, CA50, CA199are sensitive to diagnose the cholangiocarcinoma. Although theconcentration of the biological markers mentioned above is high in the blood of patients,their specificity and sensitivity to the early stages of the patient is poor. So the diagnosis ofcholangiocarcinoma of early stage is especially important.Polysaccharides, protein, nucleic acid are three most inmpotant large moleculethat constitute organism. Multicellularity sugar chains covered a wide range of biologicalsignifycance, such as the development and differentiation of the cell and form of maintain-ing and participating in the cellular immune and cell between recognition, antigen of bloodtype and biological markers of malignant cells.The sugar chain of glycoprotein plays animportant role in the protein folding, transportation and positioning. The change of sugarchains is also the cause of a variety of disease related with acute or chronic inflammatorydisease, autoimmune disease, cancer and other diseases occurrence and in the developmentof theses diseases the change of the glycoprotein sugar chains is very common. So thechange of the abnormal sugar is expected to become a non-invasive and early diagnosis of cholangiocarcinoma. DNA sequencer-assisted fluorophore—assisted carbohydrateelectrophoresis (DSA-FACE) was proved in the previous study to be a rapid, highlysensitive and high throughput method for N-glycome profiling, making it is available toapply N-glycomics to clinical diagnosis and prediction of CCA. The present study is toassess the diagnostic value of N-glycan in large sample clicinal case control study.Micro RNA (microRNAs, miRNAs) is a kind of endogenous coding smallmolecular RNA,and its length is about21to25nucleotide, existing widely in eukaryotes.Through the base pairing with the target genes,it can degradate mRNA or inhibit thetranslation of target genes, so that it participates in several important biological processesuch as the gene expression of psottranscriptional regulation. Many studies have showedthat many miRNAs plays a very important role in the development of several humantumors such as primary liver cancer, stomach cancer, small cell lung cancer and pancreaticcancer. The expression of the miRNA change not only in tissue but aoso in peripheralblood cycle and the changing in the blood is stable. These changes are closely related withthe occurrence and development of cancer so it can be as tumor markers to diagnose thedisease in the early stage. The detection of tumor-specific miRNA in peripheral bloodplays a crucial role in the tumor early diagnosis and treatment.Part1: N-glycomic study in primary cholangiocarcinoma patientsThis study aimed to assess the diagnostic value of N-glycan based diagnostic model inHCCA identification. A total of98subjects including44HCCA,9congenital bile ductcyst,17gallstones and28healthy controls were recruited. N-glycome of serumglycoprotein was profiled by DSA-FACE. We apply completely random variance analysisand evaluation of the index ROC curves to decide their diagnostic efficacy. The resultsreveal that two N-sugar chains(peak10, Peak9) can be used as a specific diagnositicmarker of cholangiocarcinoma and Peak1and peak2can be used as the bile duct cysttumor-specific markers. Peak10and CA19-9are more effective to diagnose thecholangiocarcinoma, the AUC were greater than0.8. CA199-9is more effective indistinguishing the cholangiocarcinoma from the health controls than peak10, but peak10ismore effective in distinguishing the cholangiocarcinoma from cyst and gallstones. Peak1ismore effective in the diagnosis of bile duct cyst. Conclusion: peak10may as a novelnon-invasive biological marker to dignose the cholangiocarnoma and peak1also can beused as a specific diagnosis of bile duct cyst and progression monitoring. Part2: microRNA study in primary cholangiocarcinoma patientsThis study aimed to assess the diagnostic value of microRNAs based diagnosticmodel in HCCA identification. A total of98subjects including44HCCA,34Bile ductbenign disease and20healthy controls were recruited. According to former researchs5microRNAs were selected, named miR-21,miR-106a,miR-224,miR-224-2,miR-370,they werw profiled by reverse transcription (RT) and quantitative PCR (qPCR). We applycompletely random variance analysis and evaluation of the index ROC curves to decidetheir diagnostic efficacy. The result showed that two microRNAs(mir-21,mir-106a) wereuseful as cholangiocarcinoma markers. Mir-21can distinguish the cholangiocarcinomafrom not only the health controls but also fome bile duct benign disease, and mir-106a candistinguish the cholangiocarcinoma from the health controls.But they are not significientdifference in different type of cholangiocarcinoma and in groups of lymph node metastasisand not. Conclusion: miR-21andmiR-106a are expected to become the cholangiocarcinomanon-invasive diagnostic markers and progression monitoring.From the present study, we concluded that abnormal fucosylation and mirRNAs areclosely associated with cholangiocarcinoma development, N-glycan and mirRNA showedgreat value in diagnosis and monitoring progression of cholangiocarcinoma. The arepromising to be a noninvasive serum maker in cholangiocarcinoma diagnosis. |
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