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全外顯子測序pNO胸段食管鱗癌術(shù)后復發(fā)的研究

發(fā)布時間:2018-04-04 23:11

  本文選題:食管鱗癌 切入點:pT1b-4aN0M0 出處:《上海交通大學》2015年博士論文


【摘要】:pN0食管鱗癌患者術(shù)后有30%~50%在5年內(nèi)復發(fā),依據(jù)腫瘤TNM分期預測預后缺乏敏感性與準確性,探索預測pN0食管鱗癌術(shù)后復發(fā)的分子生物學標志物,具有臨床重要意義。本課題包括以下二部分:1.全外顯子測序食管鱗癌淋巴結(jié)轉(zhuǎn)移相關(guān)基因突變研究目的:篩選與食管鱗癌淋巴結(jié)轉(zhuǎn)移密切相關(guān)的基因突變。方法:取2例食管鱗癌患者原發(fā)腫瘤、轉(zhuǎn)移淋巴結(jié)、正常食管組織進行全外顯子組測序,并進行Sanger擴大驗證。結(jié)果:篩選出原發(fā)腫瘤及轉(zhuǎn)移淋巴結(jié)中存在而正常食管組織中不存在的2個基因2個雜合突變位點:CXCR1上的c.251CT(p.A84V)和PABPC1上的c.1672CG(p.Q558E),經(jīng)預測軟件分析這2個突變位點都是高致病性的。結(jié)論:CXCR1上的c.251CT(p.A84V)和PABPC1上的c.1672CG(p.Q558E)2個雜合突變位點可能是食管鱗癌淋巴結(jié)轉(zhuǎn)移的新的致病突變。2.p N0胸段食管鱗癌術(shù)后復發(fā)及生存相關(guān)因素研究目的:探索pN0食管鱗癌術(shù)后復發(fā)及生存相關(guān)因素。方法:檢測112例pT1b-4aN0M0胸段食管鱗癌原發(fā)腫瘤中CXCR1、PABPC1的突變情況,用Logistic及COX回歸等方法分析臨床病理學因素及突變基因與術(shù)后復發(fā)及生存的關(guān)系。結(jié)果:17例患者檢測到CXCR1突變,其中11例患者發(fā)生術(shù)后復發(fā);8例患者檢測到PABPC1突變,4例患者發(fā)生術(shù)后復發(fā)。Logistic多因素分析發(fā)現(xiàn)CXCR1突變、腫瘤分化程度、病變長度、腫瘤部位顯著影響術(shù)后總體復發(fā),CXCR1突變、腫瘤分化程度顯著影響術(shù)后局部區(qū)域性復發(fā),病理分期顯著影響術(shù)后遠處轉(zhuǎn)移;COX多因素分析發(fā)現(xiàn)腫瘤分化程度、病變長度、年齡顯著影響術(shù)后無瘤生存(disease-free survival,DFS),T分期、CXCR1突變、腫瘤分化程度、年齡、腫瘤部位顯著影響術(shù)后總體生存(overall survival,OS);PABPC1不影響pT1b-4aN0M0食管鱗癌術(shù)后復發(fā)。結(jié)論:1)CXCR1突變與pT1b-4aN0M0食管鱗癌術(shù)后復發(fā)、生存密切相關(guān),CXCR1突變可能是pT1b-4aN0M0食管鱗癌術(shù)后淋巴結(jié)轉(zhuǎn)移的致病基因;2)CXCR1突變、腫瘤分化程度、病變長度、腫瘤部位是pT1b-4aN0M0食管鱗癌術(shù)后總體復發(fā)的獨立預測因素;3)CXCR1突變、腫瘤分化程度是術(shù)后局部區(qū)域性復發(fā)的獨立預測因素,病理分期是術(shù)后遠處轉(zhuǎn)移的獨立預測因素,我們推測pT1b-4aN0M0食管鱗癌術(shù)后局部區(qū)域性復發(fā)和遠處轉(zhuǎn)移具有不同的路徑;4)CXCR1突變、T分期、腫瘤分化程度、年齡、腫瘤部位是術(shù)后OS的獨立預后因素,腫瘤分化程度、病變長度、年齡是術(shù)后DFS的獨立預后因素。
[Abstract]:30% of patients with pN0 esophageal squamous cell carcinoma recurred within 5 years after operation. It is of great clinical significance to explore molecular biomarkers for predicting recurrence of pN0 esophageal squamous cell carcinoma by TNM stage.This topic includes the following two parts: 1.Study on mutation of lymph Node Metastasis-associated genes in esophageal squamous Cell carcinoma by Total Exon sequencing objective: to screen gene mutations closely related to lymph node metastasis of esophageal squamous cell carcinoma.Methods: two patients with esophageal squamous cell carcinoma were selected and the metastatic lymph nodes and normal esophageal tissues were sequenced and verified by Sanger.Results: two heterozygous loci were screened in primary tumors and metastatic lymph nodes but not in normal esophageal tissues. Two heterozygous loci (c.251CTA p.A84V) and c.1672CGp.Q558EN on PABPC1 were selected. The two mutation sites were highly pathogenicity by predictive software analysis.緇撹:CXCR1涓婄殑c.251CT(p.A84V)鍜孭ABPC1涓婄殑c.1672CG(p.Q558E)2涓潅鍚堢獊鍙樹綅鐐瑰彲鑳芥槸椋熺槌炵檶娣嬪反緇撹漿縐葷殑鏂扮殑鑷寸梾紿佸彉.2.p N0鑳告椋熺槌炵檶鏈悗澶嶅彂鍙婄敓瀛樼浉鍏沖洜绱犵爺絀剁洰鐨,

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