摘要
Objective:Esophageal carcinoma is the eighth most common malignant tumor and ranked the sixth cause of death in the worldwide careinoma.To find out effective serum markers for early diagnosis and targeted treatment is important to improve esophageal carcinoma survival rate.The aim of this study was to screen differ-entially expressed serum protein profiling in esophageal squamous cell careinoma(ESCC)patients with differ-ent Chinese medicine syndrome and establish ESCC syndrome diagnosis model,to explore the signifcance of ESCC serum differential protein in traditional Chinese medicine(TCM)syndrome diagnosis and provide exper-imental and theoretical basis for the diagnosis,clinical treatment of ESCC.Methods:Serum specimens of 80 ES-CC patients with different syndrome and 20 healthy people were selected according to distribution of their sex and age.Magnetic beads based weak cation exchange combined w ith matrix-assist ed laser desorption/ionization time-of-flight mass spectrometry prot eomic technology and Autoflex Analysis and ClinProTools software were applied to screen differentially expressed serum protein profiling.Then establishing each syndrome group diag-nosis model and verifying with new samples to evaluate the diagnosis value of each syndrome group diagnosis model.Results:18 significantly differential expression protein peaks were screened between the whole ESCC patients sera and the healthy control group.Compared with normal control group,among which,ten were signif-cant down-regulation with m/z values of4210,4267,4054,4248,2106,4091,2991,5337,3952,822,and eight were significant up-regulation with m/z values of 2900,2883,1467,1617,2862,2600,895,811.There were 16,12,11,15 differentially expressed protein peaks in phlegm and qi stagnat ion syndrome(Group P),fluid insufficiency and heat agglomeration syndrome(Group F),blood stasis syndrome(Group B),qi and yang deficiency syndrome(Group Q),respectively.Protein with m/z of4210,4091,4054 and 5337 presen-ted obviously low expression in all syndrome groups,while protein with m/z of2883,1617 presented obvious-y high expression.Protein with m/z of 4644 is an obvious and significative biomarker in the comparison of dif-ferent syndrome of ESCC.Establishing ESCC each syndrome serum different ial protein profiling diagnosis mod-el showed that the specificity and veracity in four syndrome groups were all≥80.00%.Conclusion:Our study achieved differentially expressed protein profiling in ESCC patients with different TCM syndromes,established relatively high sensitivity and specificity of different syndrome of ESCC serum differential protein profiling diag-nosis model,which implied the screened syndrome related serum differential expression protein in TCM syn-drome differentiation and diagnosis had great clinical meaning,could be the assistant diagnosis biomarker of ESCC.
目的:食管鳞状细胞癌是世界第八大最常见的恶性肿瘤,致死率居世界第六位。寻找有效的早期诊断和靶向治疗血清标志物对于提高食管鳞状细胞癌生存率非常重要。本研究旨在筛选不同中医证型食管鳞癌(ESCC)患者血清差异表达蛋白谱,并建立ESCC证型诊断模型,探讨食管鳞癌血清差异表达蛋白在中医证候诊断中的意义,为食管鳞癌的诊断、临床治疗提供实验和理论依据。方法:根据性别年龄分布选择80例不同证型的ESCC患者和20例健康正常人,收集血清标本。应用交换弱阳离子磁珠(MB-WCX)联合基质辅助激光解吸/电离飞行时间蛋白质谱(MALDI-TOF-MS)技术,采用Autoflex Analysis和ClinProTools软件筛选不同证候血清差异表达蛋白谱。建立食管鳞状细胞癌各证候组诊断模型,并用新的样本进行验证,以评价各证候组诊断模型的诊断价值。结果:从健康对照组和ESCC患者组的血清样本中筛选出18个具有显著差异表达的蛋白质,与健康对照者相比,10个蛋白质显著下调,m/z值为4210、4267、4054、4248、2106、4091、2991、5337、3952、822;8个蛋白质显著上调,m/z值为2900、2883、1467、1617、2862、2600、895、811。从食管鳞状细胞癌痰气交阻证(P组)、津亏热结证(F组)、瘀血内结证(B组)、气虚阳微证(Q组)血清中分别筛选出16个、12个、11个、15个差异蛋白峰,m/z为4210、4091、4054、5337的蛋白质在各证型组中均呈明显低表达,m/z为2883、1617的蛋白质在各证型组中均呈明显高表达。m/z为4644的蛋白在ESCC不同证候比较中是一个明显而有意义的生物标志物。建立ESCC各证候血清差异蛋白谱诊断模型,检测4个证候组的特异性和灵敏性均≥80.00%。结论:本研究获得了不同中医证型ESCC患者的差异表达蛋白谱,建立了具有较高敏感性和特异性的不同证型ESCC血清差异蛋白谱诊断模型,提示筛选的证候相关血清差异表达蛋白在中医辨证诊断中具有重要的临床意义,可作为ESCC辅助诊断的生物标志物。
基金
We thank for the fun-ding support from the Excellent project of Na-tional Returned Scholars Funds[(2007)170]
National Natural Science Foundation of China(30873220,30973698,81550014)。
