应用ClinProt系统分析食管癌家族史相关血清蛋白表达谱  

Analysis of protein expression spectrum related to esophageal cancer family history by ClinProt system

作　　者：李秀敏[1] 赵志敏[1] 许洁[1] 常廷民[1] 崔娟[1,2] 申芳芳[1,2] 周福有[2,3] 王建坡[2,3] 常扶保 王立东[1,2] 

机构地区：[1]新乡医学院癌症研究中心,河南新乡453003 [2]郑州大学第一附属医院河南省食管癌重点开放实验室,河南郑州450052 [3]安阳市肿瘤医院,河南安阳455000 [4]林州市中心医院胸外科,河南林州456592

出　　处：《河南大学学报（医学版）》2012年第3期191-196,共6页Journal of Henan University:Medical Science

基　　金：国家科技部863重大项目(2012AA02A503);国家自然科学基金(30971133);河南省卫生科技创新人才项目(3047)

摘　　要：目的寻找可能与食管癌患者食管癌家族史相关的血清标志物。方法收集林州及其周边食管癌高发区食管癌家族史阳性食管癌患者28例和食管癌家族史阴性食管癌患者38例血清样本,经Clinprot磁珠纯化、基质辅助激光解析电离飞行时间质谱(MALDI-TOF-MS)分析建立相应的蛋白质指纹图谱,应用ClinProTools生物信息学方法研究其血清蛋白表达谱。比较食管癌家族史阳性和阴性的食管癌患者血清蛋白表达谱,筛选出可能与食管癌家族史相关的差异蛋白。每组样品采用sigma血清进行批间重复性检测。结果平均CV值为0.232;在相对分子质量800～10 000范围内,共检测到家族史阳性与阴性食管癌患者血清差异蛋白101个。选取组合分组能力最好的5个质荷比(M/Z)分别为5 248.24、5 905.05、2 023.12、2 953.07、4 467.16的蛋白峰建立模型并验证,显示食管癌家族史阳性组和阴性组的血清差异蛋白表达无显著性差异(P>0.05)。对食管癌家族史阳性组与阴性组进行分析,采用GA(遗传算法)模型算法选取差异蛋白,识别率为82.62%;准确性为家族史阳性组69.23%,家族史阴性组96%;预测能力为61.89%;采用SNN(遗传算法)选取差异蛋白,食管癌家族史阳性组及阴性组识别率和准确性均为100%,预测能力为53.25%。结论应用ClinProt系统未检测到与食管癌家族史相关的特异性蛋白质,推测食管发生癌变后所产生的反应蛋白可能与食管癌家族史无明显相关性。要寻找食管癌发生及家族聚集的原因,还需要对更多因素进行进一步分析、检测以及大样本的分子流行病学研究。Objective To seek for the serum protein biomarkers related to esophageal cancer hereditary susceptibility of esophageal cancer patients in high esophageal cancer incident area.Methods the subjects were 66 esophageal cancer patients from high esophageal cancer incident area.Among them,there were 28 patients with esophageal cancer family history and 38 patients without esophageal cancer family history.All patients’ serums were collected.By Clinprot magnetic bead purification,matrix-assisted laser desorption/ionization time of flightmass spectrometry（MALDI-TOF-MS） to analyze corresponding protein finger print,We applied ClinProTools bioinformatic methods to study serum protein spectrum,and to compare serum protein expression spectrum in family history positive esophageal cancer patients with that in family history negative esophageal cancer patients and to screen the expected protein related to the hereditary susceptibility of esophageal cancer.Sigma serum was used in every sample to repeat the detection.Results We used mean coefficient of variability（CV） to assess repeatability,and mean CV was 0.232.In the range of relative molecular mass between 800 and 10 000 Da,101 proteins were detected in family history positive esophageal cancer patients and family history negative esophageal cancer patients.Five proteins with the strongest combination and subgroup ability group were chosen as category variable to establish category predictive model,which mass charge ratio（M/Z） was 5 248.24,5 905.05,2 023.12,2 953.07 and 4 467.16.We tested it and found the differential protein expression have no difference in family history positive esophageal cancer patients and family history negative esophageal cancer patients（P〉0.05）.We used GA（heredity algorithm） algorithm to select differential protein,recognition rate in family history positive esophageal cancer patients and family history negative esophageal cancer patients was 82.62%.Accurate rate was 69.23% in family history positive esophageal cancer patient

关 键 词：液体蛋白芯片飞行时间质谱系统 食管癌 家族史 遗传易感性 

分 类 号：R735.1[医药卫生—肿瘤]