本文選題：胰腺囊性腫瘤 + 黏液性囊腺瘤�。� 參考：《中國人民解放軍醫(yī)學院》2017年博士論文

【摘要】：目的:通過采用超聲內(nèi)鏡下細針穿刺活檢能夠為胰腺囊性腫瘤的診斷提供直觀的第一手資料,對腫瘤中發(fā)生基因突變的改變、蛋白質(zhì)糖基化改變的進行初步的檢測。方法:本實驗主要分四部分進行:1.按病理類型將課題入組的胰腺囊性腫瘤患者分為高危組與低危組,選用多因素logistic回歸分析低危組與高危組臨床數(shù)據(jù)。2.對胰腺囊性腫瘤囊液進行DNA提純,分析所選取的熱點突變基因KRAS、GNAS、CTNNB1、BRAF在各類型中的突變情況。3.分析兩大類型的胰腺囊性腫瘤,漿液性囊腺瘤與黏液性囊腺瘤囊液中蛋白質(zhì)糖基化的變化情況:凝集素芯片技術(shù)比較漿液性/黏液性囊腺瘤囊液糖蛋白糖鏈譜。4.通過存在差異的凝集素富集,LC-MS/MS分析比較來自(N-linked)蛋白質(zhì)肽段;完成蛋白質(zhì)鑒定、通過生物信息學注釋,及String蛋白相互作用圖,尋找參與黏液性胰腺囊性腫瘤改變的通路和關(guān)鍵蛋白。結(jié)果:1.腫瘤的最長徑≥2.5cm,主胰管≥5mm考慮為胰腺囊性腫瘤的危險因素。通過非參數(shù)秩和檢驗,囊液的CEA, CA19-9,CA72-4在低危組與高危組存在明顯差異,結(jié)果顯示脂肪酶≥1038.05ng/ml時,CEA≥10.33ng/ml時,診斷高危胰腺囊性腫瘤準確率為78.4%,有72.2%的敏感性和82.1%的特異性。2. 3例IPMN病例中其中1例KRAS基因12、13位點密碼子的突變激活,Gly12CysGGTGTT,病理:胰腺導管內(nèi)乳頭狀黏液性腫瘤(IPMN),部分上皮輕-中度不典型增生。10例MCN病例中其中1例CTNNB1突變熱點為編碼區(qū):32/33/34/37密碼子,34位點GGACGA,37位點TCTTCC,病理:胰腺(體尾部)黏液性囊腺瘤伴輕度不典型增生�；蛲蛔儥z測可對胰腺囊性腫瘤的惡變起輔助診斷的意義。3. 6種凝集素(如STL、WGA、BPL、DBA、PTL-I、MAL-Ⅰ)識別糖鏈分別在胰腺囊性腫瘤中表達上調(diào)或下調(diào)。4.通過String蛋白相互作用分析,主要涉及代謝通路,PI3K-ATK 通路(YWHAZ,YWHAG,YWHAQ,LAMC1),處于交叉點核心的蛋白 YWHAZ,YWHAG,YWHAQ, ACTB, SPA5, S100A11均屬于關(guān)鍵蛋白是參與黏液性胰腺囊性腫瘤改變的關(guān)鍵蛋白。結(jié)論:通過多個維度的對胰腺囊性腫瘤進行客觀的診斷分析,研究胰腺囊性腫瘤相關(guān)糖蛋白糖鏈的變化,有助于尋找靈敏度和準確度更高的腫瘤標志物,進一步揭示胰腺囊性腫瘤進展的糖生物學機制并為研發(fā)新的治療方法提供有價值信息。
[Abstract]:Objective: through the use of ultrasound-guided fine needle aspiration biopsy for the diagnosis of cystic tumor of the pancreas, the first hand data can be provided for the change of the gene mutation and the change of protein glycosylation in the tumor. Methods: this experiment is divided into four parts: 1. the cystic swelling of the pancreas in the group according to the pathological type The patients were divided into high risk group and low risk group. Multiple factor Logistic regression analysis was used to analyze the DNA purification of cystic fluid of pancreatic cystic tumor by.2. in low risk group and high risk group. Analysis of the selected hot mutation gene KRAS, GNAS, CTNNB1, BRAF in all types of mutations,.3. were divided into two types of pancreatic cystic tumors and serous cystadenoma. Changes in protein glycosylation in the cystic fluid of mucinous cystadenoma: the agglutinin chip technique compared the glycoprotein glycosyl chain.4. of the serous / mucinous cystadenoma with a differential agglutinin enrichment, LC-MS/MS analysis and comparison of the protein peptide from (N-linked), the identification of white matter, the bioinformatics annotation, and the String eggs. Results: the longest diameter of the 1. tumor was more than 2.5cm, and the main pancreatic duct more than 5mm was considered as a risk factor for pancreatic cystic tumors. The CEA, CA19-9, and CA72-4 of the fluid were significantly different in the low risk group and the high risk group by the nonparametric rank sum test. The results showed fat. When the enzyme was more than 1038.05ng/ml, when CEA was more than 10.33ng/ml, the accuracy of diagnosis of high risk pancreatic cystic tumors was 78.4%, with 72.2% sensitivity and 82.1% specific.2., of which 1 cases of KRAS gene 12,13 codon mutations were activated, Gly12CysGGTGTT, pathological: intraductal papillary mucinous tumor (IPMN), partial epithelial light to moderate. Among the cases of atypical hyperplasia, 1 cases of.10 MCN cases, CTNNB1 mutation hot spots are coded regions: 32/33/34/37 codon, 34 site GGACGA, 37 loci TCTTCC, pathology: mucinous cystadenoma of the pancreas (body tail) with mild atypical hyperplasia. Gene mutation detection can assist the diagnosis of pancreatic cystic neoplasia.3. 6 agglutinin (such as STL, WGA, BPL). DBA, PTL-I, MAL- I) recognize that the sugar chains are up-regulated and down regulated in cystic tumors of the pancreas, respectively, and.4. through String protein interaction analysis, mainly involved in the metabolic pathway, the PI3K-ATK pathway (YWHAZ, YWHAG, YWHAQ, LAMC1), and the protein YWHAZ at the core of the intersection. Conclusion: the objective diagnosis and analysis of cystic tumor of the pancreas by multiple dimensions and the study of the changes of glycoprotein glycate chain related to cystic tumor of the pancreas can help to find the tumor markers with higher sensitivity and accuracy, and further reveal the sugar biological mechanism of the progress of pancreatic cystic neoplasms. New methods of treatment provide valuable information.
【學位授予單位】：中國人民解放軍醫(yī)學院
【學位級別】：博士
【學位授予年份】：2017
【分類號】：R735.9

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