段宝军,白 俊,张 琰.质谱筛选结直肠癌潜在血清标志物的研究 (撤回稿件)[J].中国肿瘤,2018,27(8):619-625.
质谱筛选结直肠癌潜在血清标志物的研究 (撤回稿件)
Study of Mass Spectrometry for Screening Potential Serum Biomarker in Colorectal Cancer Patients
投稿时间:2018-01-18  
DOI:10.11735/j.issn.1004-0242.2018.08.A011
中文关键词:  结直肠肿瘤  质谱  血清标志物
英文关键词:colorectal neoplasms  mass spectrometry  serum biomarker
基金项目:
作者单位
段宝军 陕西省人民医院 
白 俊 陕西省人民医院 
张 琰 陕西省人民医院 
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中文摘要:
      摘 要:[目的] 运用弱阳离子磁珠(MB-WCX)联合基质辅助激光解吸离子飞行时间质谱(MALDI-TOF MS)筛选结直肠癌的血清学标志物。[方法] 收集健康对照(24名)、结直肠癌患者(24例)的血清标本。弱阳离子磁珠分离血清小分子蛋白,MALDI-TOF MS建立健康对照和结直肠癌患者血清蛋白表达谱。Clinprot Tools 2.0软件分析差异表达峰,液相色谱-电喷雾离子化质谱(LC-ESI-MS/MS)鉴定差异表达蛋白。另收集结直肠癌及健康对照样本,ELISA法(各38例)验证血清差异表达蛋白,免疫组化(各40例)验证组织差异表达蛋白。生物信息学分析差异表达蛋白与结直肠癌临床病理特征之间的关系。[结果] 共发现67个差异表达峰,10个有显著差异(P<0.000001),在结直肠癌中高表达6个,低表达4个,其中m/z:4793.25及m/z:2663.45的差异表达峰经鉴定分别为组蛋白赖氨酸甲基转移酶(SETD7)和纤维蛋白原α前体亚型1(FGA)。结直肠癌患者血清中SETD7蛋白水平较健康对照升高(P=0.000),结直肠癌较癌旁组织中SETD7阳性细胞增多(P=0.003)。生物信息学分析提示SETD7基因表达在结直肠癌组织中显著上调(P=0.008),且其表达水平与T分期有关(P=0.019)。[结论] 结直肠癌患者与健康对照者血清质谱差异明显,SETD7有望成为新的结直肠癌血清标志物。
英文摘要:
      Abstract:[Purpose] To screen the serum biomarkers for colorectal cancer. [Methods] The serum samples of healthy control(control,n=24) and colorectal cancer(CRC,n=24) were collected. Peptidome of all samples were extracted by magnetic beads based weak cation exchange(MB-WCX) chromatography and detected by matrix assisted laser desorption ionization time of flight mass spectrometry(MALDI-TOF MS). The proteomic profile was analyzed by ClinProtTools software 2.0,and the differentially expressed peptides were identified by liquid chromatography-eletronic spray ionization mass/mass(LC-ESI-MS/MS). ELISA(control,n=38 and CRC,n=38) and immunohistochemi-stry(control,n=40 and CRC,n=40) assay were used to validate the differently expressed peptides in serum and tissue respectively. Bioinformatics were used to analyze the relationship between diffe-rentially expressed peptides and clinicopathology features of CRC. [Results] Sixty seven m/z peaks were distinguished between control and CRC groups,and 10 peaks were significantly different(P<0.000001). Compared with control group,6 peaks were up-regulated and 4 peaks were down-regulated in CRC. Two peaks(m/z:4793.25 and m/z:2663.45) were identified as histone-lysine N-methyltransferase(SETD7) and isoform 1 of fibrinogen alpha chain precursor(FGA). Compared with control group,the expression of SETD7 was significantly higher in serum(P=0.000) and tissue(P=0.003) of CRC patients. Bioinformatics showed that SETD7 expression was up-regulated in CRC(P=0.008),and was significantly related to the T stage(P=0.019). [Conclusion] The proteomic profiles of control and CRC groups are significantly different,and SETD7 is expected to be a novel serum biomarker for CRC.
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