肝细胞性肝癌患者介入治疗前后血清蛋白质组的变化.doc

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1、肝细胞性肝癌患者介入治疗前后血清蛋白质组的变化【摘要】　　目的用表面增强激光解吸离子化飞行时间质谱(surface-enhancedlaserdesorption-ionizationtime-of-flightmassspectrometry,SELDI-TOF-MS)蛋白质芯片检测肝细胞性肝癌(简称肝癌)患者介入治疗前后血清蛋白质组的变化，初步探讨肝癌介入治疗的药物靶点。方法应用SELDI-TOF-MS蛋白质芯片检测50例未经治疗的肝癌患者、50例介入治疗的肝癌患者，获得弱阳离子交换芯片(weakcationicexchanger)蛋白表达图谱，BioMarkerWizard软件

2、分析差异蛋白。结果未经治疗的肝癌患者和介入治疗的肝癌患者血清中检测到不同质荷比处有3个差异蛋白质峰，其蛋白质含量差异有统计学意义(P<0.05)。数据库搜索这3个蛋白质峰，得到3种与之分子量最为接近的蛋白质。　结论　应用SELDI-TOF-MS筛选肝癌患者介入治疗的药物靶点快速、有效，检测到的3个差异蛋白质可能是肝癌患者介入治疗的药物靶点。【关键词】肝细胞性肝癌蛋白质组学药物靶点SELDI蛋白质芯片　　Abstract:ObjectiveTodetecttheserumproteomicpattersinhepatocellularcarcinoma（HCC）patientst

3、reatedbyinterposechemotherapybyusingSELDI-TOF-MS（surface-enhancedlaserdesorption-ionizationtime-of-flightmassspectrometry）proteinchiparraytechnology,screendrugtargets,evaluateitsclinicalsignificance.Methods50casesofthepatientswithhepatocellularcarcinomawithoutreceivinganytherapy,50casesofthepat

4、ientswithhepatocellularcarcinomareceivingtheinterposechemotherapyweretestedbyweakcationicexchangerproteinchipandsurface-enhancedlaserdesorption-ionizationtime-of-flightmassspectrometry.ThediagnosticmodelsweredevelopedandvalidatedbyBioMarkerWizard.ResultsAtthedifferentM/Zvaluerange,threeproteins

5、wereobviouslydifferentinthegroupofthepatientswithhepatocellularcarcinomawithoutreceivinganytherapy,thepatientswithhepatocellularcarcinomareceivingtheinterposechemotherapy.Throughsearchingdatabaseswehavegotthreeprobablysignificantproteinsrelatedwiththem.ConclusionsDetectionofserumproteomicpatter

6、sforhepatocellularcarcinomatreatedbyinterventionaltherapyusingSELDI-TOF-MSproteinchiparrayisquickandeffective.Thesedifferentialproteinscouldbedrugtargetsofhepatocellularcarcinomabeforeandaftertheinterposechemotherapyintheserum.　　Keywords:HepatocellularCarcinoma;Proteomics;Drugtargets;SELDI;Prot

7、einChip5　　目前肝癌发病率在我国呈上升趋势，其死亡率占恶性肿瘤死亡率的前列，每年新发肝癌病例约11.02万例，占全世界发病人数42.5%。一些肝癌尤其是多发性或大肝癌往往丧失手术机会而选择经肝动脉介入治疗，而寻找介入治疗的药物靶点对于进一步提高肝癌临床治疗水平具有重要意义[1]。近年来，蛋白质组学研究发展迅猛，它旨在整体水平上研究细胞或组织内蛋白质组成及其活动规律。表面增强激光解吸电离(SELDI)蛋白质芯片技术是近几年迅速发展起来的一种蛋白质组学