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1、肺腺癌患者血清生物标志物筛选探究【摘要】目的采用SELDI-TOF-MS技术探讨肺腺癌患者血清蛋白标志物,并建立一个稳定、简便、快速的实验方法。方法肺腺癌患者321例和正常对照人群321例,按照年龄、性别、吸烟史的有无进行1:1配对,采用WCX2芯片技术进行血清蛋白质组学研究,用蛋白芯片阅读器PBSII对芯片进行扫描、分析。结果肺腺癌患者血清蛋白图谱与正常对照组相比,存在15个差异表达蛋白(P<;10-5),其中包括11个高表达蛋白,分子量分别是1860Da.4055%、4195Da.4211Da.4959D
2、a、5329Da.5980Da.6313Da.6880Da.7762Da、9281Da,4个低表达蛋白,分子量分别是2564Da、2932Da、3082Da、3442Dao显著高表达的潜在标志物5个,相对分子量分别为4055Da、421IDa、4959D&、5329Da和7762Da,以峰值比1.5为界值时,其诊断肺腺癌的灵敏度分别为90.41%,78.08%、50.68%、57.53%、72.60%,特异度分别为97.06%、93.44%.71.15%、76.36%、94.92%,选用4055Da.4211Da
3、.4959Da、5329Da和7762D&建立决策树模型对样品进行筛选验证,其准确率为85.00%,灵敏度为86.67%,特异度为83.33%o结论用该技术能筛选出灵敏度和特异性较好的差异表达蛋白,为肺腺癌的早期发现提供了一种新的、无创伤的实验方法,可能具有较好的临床应用前景。【关键词】肺腺癌;生物标志物;SELDI-TOF-MS;蛋白质组学ThescreeningstudyonlungadenocarcinomaserumbiomarkersbySELDI-TOF-MS[Abstract】ObjectiveTo
4、selectrelativespecificbiomarkersinserumfromlungadenocarcinomapatientsusingsurface-enhancedlaserdesorptionandionizationtimeofflightmassspectrometry(SELDI-TOF-MS)proteinchiptechnology.MethodsSerumsamplesfrom321lungadenocarcinomapatients,321healthyvolunteerswith
5、matchedgender,ageandhistoryofsmokingwereanalyzedusingWCX2poteinchiptoscreeningpotentiallybiomarkers・Proteomicspectraweregeneratedbymassspectrometry.ResultsFivehighlyexpressedpotentialbiomarkerswereidentifiedwiththerelativemolecularweightsof4055Da,421IDa,4959D
6、a,5329Daand7762Da.Thesensitivityfordiagnosinglungadenocarcinomawas90.41%,78.08%,50.68%,57.53%,72.60%;andspecificitywas97.06%,93.44%,71.15%,76.36%,94.92%,whenthecriticalpointwasmade1.5.Thesensitivityfordiagnosinglungadenocarcinomawas86.67%,andspecificitywas83.
7、33%byappliedtothisproteinfingerprintspatternvalidation・ConclusionSELDI-TOF-MSproteinchiptechnologyisaquick,easy,convenient,andhigh-throughputanalyzingmethodcapableofselectingseveralrelativelyspecific,potentialbiomarkersfromtheserumoflungadenocarcinomapatients
8、andmayhaveattractiveclinicvalue・[Keywords】lungadenocarcinoma;biomarkers;SELDI-TOF-MS;proteomics肺癌是目前全球发病率最高的恶性肿瘤之一,对人类健康的危害日益严重。目前,肺癌早期诊断困难。80%肺癌患者就诊时已属晚期,失去了手术根治的机会,放疗化疗效果不佳,5年生存率不到15%;而