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胃癌相关血清标志分子的筛选与初步应用

The identification and preliminary application of the tumor associated marker molecular in the serum of gastric cancer patients

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【作者】 薛文成冯凯孟冬娅郑燕华张建中康辉辛彦

【Author】 Xue Wen-Cheng Feng Kai Meng Dong-Ya et al. Fourth Laboratory, Cancer Institute, China Medical University, Shenyang110001, China.

【机构】 中国医科大学第一附属医院肿瘤研究所解放军306医院

【摘要】 目的:探讨血清蛋白质指纹图谱技术用于胃癌相关血清标志分子筛选的可行性。方法:用WCX2(弱阳离子交换芯片)蛋白芯片结合表面增强激光解吸电离飞行时间质谱 (SELDI-TOF-MS)技术检测57例胃癌患者,30例健康者、7 例胃良性病患者、9例除胃以外的消化道癌肝转移患者血清蛋白指纹图谱,通过比较分析各组蛋白质指纹图谱差异,筛选与胃癌相关的血清标志分子。采用Ciphergen公司Biomarker Patterns Software初步建立早期胃癌预警决策树分类器模型并进行盲筛验证。结果:初步筛选出与早期胃癌相关的血清蛋白质42种,其中27种蛋白质在早期胃癌中低表达,15种在早期胃癌中高表达。初步建立了3个对早期胃癌诊断预警分类效果较好的模型,参加盲筛的9例早期胃癌患者均披准确鉴别。3个模型对27例胃癌患者(含9例早期胃癌患者)、7例胃良性病患者、19例健康者进行盲筛试验验证,盲筛结果以模型Ⅱ的分类效果最为理想,结果27例胃癌诊断正确率为96. 3%(26/27),仅有1例被误判为非癌,19例健康者诊断正确率为100%(19/19),7例胃良性病变诊断正确率为42.9%(3/7), 有4例被误判为胃癌。所有3个模型的总体敏感性96.3%,特异性73.1%~84.6%,阴性预测值94.7~95.7%,阳性预测值78.9~86.7%。筛选出16种胃癌肝转移与其它消化道癌肝转移血清差异蛋白,其中6196、4887、10260、9288M/Z四种蛋白质在胃癌组患者中显著高于正常对照组(P<0.001)。结论:血清蛋白质指纹图谱技术可有效筛选出胃癌相关的血清标志分子,有进一步研究的价值。

【Abstract】 Objective: To detect specific protein biomarkers in serum of the gastric cancer arising with the serum protein fingerprints technology. Method: Using surface-enhanced laser desorption ionization mass spectrom-etry (SELDI/TOF-MS) and Protein-Chip technology, coupled with a pattern-matching algorithm and serum samples, we screened differential protein in differentiate gastric cancer patients, non-cancer patients, healthy blood-donors. Result: There were 42 different proteins, among them 27 proteins lowly expressed and the others highly expressed in early gastric carcinoma. Three decision tree classifier models had been constructed by our study. Among 3 decision-tree classification models con- structed in the study, the most efficient one (model 3) was consist of single protein 6366M/Z. the result of test with blind set display that its sensitivity is 96.3%, specificity 84.6%, negative predicting value 95.7%, positive predicting value 86.7%, total effective rate 90.6%. Between the liver metastases derived from gastric cancers and from other digestive tract cancers, 16 different proteins were obtained. The proteins 6196 M/Z, 4887 M/Z, 10260 M/Z and 9288M/Z are more likely to be the new biomarkers identifying the liver metastasis derived from gastric cancer. Conclusion: The specific biomarkers selected with the SELDI technology could be used for early diagnosis of gastric cancer. Further study is needed to explore the potential value of clinical application in predicting occurrence of gastric cancer.

【关键词】 胃癌蛋白质谱早期诊断
【Key words】 Gastric cancerProtein profiling diagnosis
  • 【会议录名称】 第四届中国肿瘤学术大会暨第五届海峡两岸肿瘤学术会议论文集
  • 【会议名称】第四届中国肿瘤学术大会暨第五届海峡两岸肿瘤学术会议
  • 【会议时间】2006-10
  • 【会议地点】中国天津
  • 【分类号】R735.2
  • 【主办单位】中国抗癌协会、中华医学会肿瘤学分会
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