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Screening For Specific N-glycans In Pancreatic Carcinoma Serum With Dsa-face

Posted on:2011-02-08Degree:MasterType:Thesis
Country:ChinaCandidate:X LiangFull Text:PDF
GTID:2194330338980882Subject:Genetics
Abstract/Summary:PDF Full Text Request
Pancreatic carcinoma is one of the malignant tumors that has the worst therapeutic effect, because of the often late onset of clinical symptoms, low rate of early diagnosis and poor result of clinical treatment. Till now, the clinicl study is still lack of specific tumor markers. DNA sequencer assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) is a powerful high throughput, high sensitivity detection method for Glycomics and is being used in the research field of serum Glycomics of hepatology, aging and breast cancer.To find Glycomic specific tumor markers of pancreatic carcinoma, DSA-FACE was performed in 41 patients with pancreatic ductal adenocarcinoma (PDA) and 100 healthy human. The results indicated that there were significant differences in N-linked glycans between PDA patients and healthy persons. Peak 6 and Peak 14 were the most significant peaks which were picked as a new tumor marker of PDA. Taking log (p14/p6) as indicator of the ROC curve analysis, the area under ROC curve was 0.803±0.041 with 75.6% sensitivity and 77% specificity. Further analysis showed that for detection of pancreatic carcinoma early metaphase with peak 14 and peak 6, sensitivity is up to 77.8% and specificity reaches 80%. These results suggested that as the serum markers for pancreatic carcinoma specific clinical diagnosis of PDA, peak 14 and peak 6 might possibly become the Glycomics indicator.It's known that there are differences in serum profile between different sexes so we grouped according to the gender to make analysis. It is found that the peak 15 showed significant difference between male patients of PDA and the healthy male but no significant difference in female. Taking log (p15/p6) as indicator, the area under ROC curve is 0.865±0.044 with 92.6% sensitivity and 80.3% specificity. Also, the peak 10 showed significant difference between female patients of PDA and the healthy female but no significant difference in male. Taking log (p14/p10) as indicator, the area under the ROC curve is 0.925±0.047 with 71.4% sensitivity and 100% specificity. So, the peak 15 and peak 10 may be closely related to the occurrence of pancreatic carcinoma of different gender, in addition, these peaks can be also taken as different sex-specific diagnostic markers of pancreatic carcinoma.Meanwhile, for the age of high incidence of pancreatic carcinoma, the N-glycomic changes in serum were analyzed between PDA and healthy persons of the age at the cutoff 60. the appropriate PDA glycan peaks were checked for the diagnose of PDA between the age over 60 and the age below it. As the specific Glycomics indexes with the cutoff point of 60-year-old for the diagnosis of pancreatic carcinoma, it's possible that theses results may become an auxiliary index for the personalized health care and make the detection more accurate and useful.The sensitivity and specificity of the current clinical tumor markers of pancreatic carcinoma is limited and high throughput detection is impossible. In this work, with high-throughput screening technology of DSA-FACE, the specific glycan peaks were founded and it can be used as potential diagnostic markers of pancreatic carcinoma. According to gender, age and many differences cases in PDA, the Glycomics indicator for each diagnosis group were analyzed. The result should be helpful for the forecast of pancreatic carcinoma, diagnosis and personalized medical treatment and might be used as a foundation to establish clinical noninvasive, fast and convenient high-throughput diagnostic methods.
Keywords/Search Tags:PDA, DSA-FACE, serum
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