【作者】 张倩；

【导师】 张莉；

【作者基本信息】 新疆医科大学 ， 肿瘤学（专业学位）， 2019， 硕士

【摘要】 目的:应用iTRAQ技术筛选出可预测新疆汉族、维吾尔族、哈萨克族食管鳞癌患者放化疗疗效及预后的差异蛋白,并比较不同民族之间的差别。方法:1.纳入91例汉、维、哈族局部晚期及晚期食管鳞癌患者,进行正规放化疗、疗效评价及随访;同时采集治疗前、后外周血。2.应用iTRAQ技术对不同民族患者治疗前、后外周血进行蛋白质鉴定和定量,并进行生物学分析,筛选出对新疆汉、维、哈族食管鳞癌患者治疗疗效及预后有预测意义的差异蛋白。结果:1.近期疗效随访结果:疗效好组(CR+PR+SD)食管癌患者占56.04%(51/91例),疗效差组(PD)患者占43.96%(40/91例),远期疗效随访结果:OS≥3年组患者占23.07%(21/91例),OS<3年组患者占76.93%(70/91例)。2.三个民族各筛选出的差异蛋白:(1)汉族患者:(1)近期疗效好与差对比共有64个差异蛋白,其中27个上调,37个下调。(2)OS≥3年组与<3年组对比共有55个差异蛋白,其中21个上调,34个下调。(2)哈萨克族患者:(1)近期疗效好与差对比共有75个差异蛋白,其中34个上调,41个下调。(2)OS≥3年组与<3年组对比共有60个差异蛋白,其中28个上调,32个下调。(3)维吾尔族患者:(1)近期疗效好与差对比共有73个差异蛋白,其中44个上调,29个下调。(2)OS≥3年组与<3年组对比共有63个差异蛋白,其中25个上调,38个下调。3.三个民族筛选出的相同蛋白:(1)三个民族在近期疗效好及近期疗效差对比中共同出现的蛋白有9个,其中均上调的有2个(COL4A3、补体C4A),未发现有同时下调的蛋白。(2)在三个民族OS≥3年组与<3年组对比中共同出现的蛋白有10个,其中均上调的蛋白1个(血浆丝氨酸蛋白酶抑制剂),均下调的有5个(抗叶酸结合蛋白、cDNA FLJ51597、cDNA FLJ53025、免疫球蛋白重链区、不典型蛋白)。4.三个民族之间的不同差异蛋白:(1)在汉族中无特异上调或下调的蛋白;(2)仅在维吾尔族近期疗效对比与远期疗效对比中均上调的蛋白1个(透明质酸酶1),均下调的蛋白1个(免疫球蛋白Kappa链);(3)仅在哈萨克族食管癌患者近期疗效对比与远期疗效对比中均上调的蛋白1个(触珠蛋白相关蛋白),无均下调的蛋白。5.与疗效有关的蛋白:(1)预示疗效好的蛋白COL4A3、补体C4A、透明质酸酶1、触珠蛋白相关蛋白HPR。(2)预示疗效差的蛋白:免疫球蛋白Kappa链。6.与预后相关的蛋白:(1)预示预后好的蛋白:血浆丝氨酸蛋白酶抑制剂、透明质酸酶1、触珠蛋白相关蛋白HPR;(2)预示预后差的蛋白:抗叶酸结合蛋白、C反应蛋白、免疫球蛋白Kappa链。结论:1.从食管癌患者外周血中能筛选出可预测食管癌放化疗疗效及预后的差异蛋白。2.COL4A3、补体C4A、透明质酸酶1、触珠蛋白相关蛋白、免疫球蛋白Kappa链、血浆丝氨酸蛋白酶抑制剂、抗叶酸结合蛋白对于食管鳞癌患者放化疗疗效及预后的判断可能会具有潜在的价值。3.新疆汉、维、哈族食管鳞癌预测放化疗疗效及预后的差异蛋白可能不尽相同。更多还原

【Abstract】 Objective: Using iTRAQ technology to screen out differential proteins that may predict the efficacy and prognosis of chemoradiotherapy in Xinjiang Han,Uygur,and Kazakh esophageal squamous cell carcinoma,and compare the difference between different ethnic groups.Methods: 1.Recruit 91 patients with locally advanced and advanced esophageal squamous cell carcinoma of Han,Uygur and Kazak,undergone regular chemoradiotherapy,evalued efficacy and follow-up;collected blood before and after treatment.2.Using iTRAQ technology identify and quantify the protein before and after treatment in different ethnic groups,and curry out biological analysis to screen out the difference proteins that may predict the efficacy and prognosis of chemoradiotherapy in patients with esophageal squamous cell carcinoma.Results: 1.Short-term follow-up results: patients with good efficacy(CR+PR+SD)accounted 56.04%(51/91),and patients with poor efficacy(PD)accounted 43.96%(40/91).Long-term efficacy Followed-up results: overall survival≥3 years accounted 23.07%(21/91),and overall survival<3 years accounted 43.96%(40/91).2.The differential proteins screened by the three ethnic groups:(1)Han patients:(1)There are 64 differential proteins in the Short-term efficacy comparison,of which 27 are up-regulated and 37 are down-regulated.(2)There were 55 differentially expressed proteins compared overall survival≥3 years group with overall survival<3 years group,21 of which were up-regulated and 34 were down-regulated.(2)Kazakh patients:(1)There are 75 differentially expressed proteins in the Short-term efficacy comparison,of which 34 are up-regulated and 41 are down-regulated.(2)There were 60 differential proteins compared overall survival≥3 years group with<3 years group,of which 28 were up-regulated and 32 were down-regulated.(3)Uygur patients:(1)There are 73 differentially expressed proteins in the Short-term efficacy comparison,of which 44 are up-regulated and 29 are down-regulated.(2)There were 63 differential proteins compared overall survival≥3 years group with<3 years group,of which 25 were up-regulated and 38 were down-regulated.3.The same protein screened from three ethnic groups:(1)There are 9 same proteins occured in the Short-term efficacy comparison of the three ethnic groups,of which 2 are up-regulated(COL4A3,C4A),there isn’t down-regulated protein.(2)There are 10 same proteins occured in the comparison of the overall survival≥3 years and<3 years,of which 1 protein(SERPINA5)is up-regulated,and 5 are down-regulated(Anti-folate binding protein,cDNA FLJ51597,cDNA FLJ53025,immunoglobulin heavy chain region,atypical protein).4.Different proteins between the three ethnic groups:(1)there isn’t protein specifically up-regulated or down-regulated in the Han nationality.(2)One protein is up-regulated only in the comparison between the Uygur long-term efficacy groups(HYAL1),One protein down-regulated(immunoglobulin Kappa chain).(3)One protein(HPR)is up-regulated only in comparison between Kazakh long-term efficacy groups.5.Proteins related to better efficacy:(1)COL4A3,C4 A,hyaluronidase,and HPR relative to better efficacy.(2)Proteins indicating poor efficacy:immunoglobulin Kappa chain.6.Prognosis-related proteins:(1)Proteins indicating poor prognosis: SERPINA5,hyaluronidase,HPR.2)Proteins indicating poor prognosis:anti-folate binding protein,CRP,immunoglobulin Kappa chain.Conclusion:1.We can screen out the differential proteins may predict the efficacy and prognosis of esophageal cancer patients recepted radiotherapy and chemotherapy from blood.2.COL4A3,C4 A,hyaluronidase,haptoglobin-related protein,immunoglobulin Kappa chain,SERPINA5,anti-folate binding protein may have potential value to predict the efficacy and prognosis of patients with esophageal squamous cell carcinoma.3.The differential proteins ralated to efficacy and prognosis in Han,Uygur and Kazakh esophageal cancer may be different.更多还原