Identification of biomarkers for endometriosis using clinical proteomics.

Identification of biomarkers for endometriosis using clinical proteomics.
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DOI:
10.4103/0366-6999.151108
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发表时间:
2015-02-20
影响因子:
6.1
通讯作者:
Chang XH
Chang XH
中科院分区:
医学2区
文献类型:
--
作者:
Zhao Y;Liu YN;Li Y;Tian L;Ye X;Cui H;Chang XH

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我们使用ClinProt技术和蛋白质组学方法研究了子宫内膜异位症(EM)的可能生物标志物。本研究纳入50例EM患者、34例良性卵巢肿瘤患者和40例健康志愿者。采用弱阳离子交换(WCX)磁珠结合基质辅助激光解吸/电离飞行时间质谱(MS)技术获得血清蛋白质组谱。通过自行设计的随机重复模式模型验证方法和ClinProtools软件对可能的生物标志物进行分析,并采用在线液相色谱-串联质谱法对结果进行优化。(4210,5264,2660,5635和5904 Da),使用3种肽(4210,5904,2660 Da)区分EM患者和健康志愿者,具有96.67%的灵敏度和100%的特异性。我们选择了EM患者和对照组之间差异最大的4210和5904 m/z,并将其分别鉴定为ATP 1B 4片段和FGA链前体的纤维蛋白原α(FGA)亚型1/2。ClinProt可以识别EM生物标志物,最值得注意的是,它甚至可以区分早期或最小的疾病。我们在4210、5264、2660、5635和5904 Da处发现了5个稳定的峰作为潜在的EM生物标志物,其中最强的峰与ATP 1B 4(4210 Da)和FGA(5904 Da)相关;这表明ATP 1B 4和FGA与EM发病机制相关。
We investigated possible biomarkers for endometriosis (EM) using the ClinProt technique and proteomics methods. We enrolled 50 patients with EM, 34 with benign ovarian neoplasms and 40 healthy volunteers in this study. Serum proteomic spectra were generated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) combined with weak cationic exchange (WCX) magnetic beads. Possible biomarkers were analyzed by a random and repeat pattern model-validation method that we designed, and ClinProtools software, results were refined using online liquid chromatography-tandem MS. We found a cluster of 5 peptides (4210, 5264, 2660, 5635, and 5904 Da), using 3 peptides (4210, 5904, 2660 Da) to discriminate EM patients from healthy volunteers, with 96.67% sensitivity and 100% specificity. We selected 4210 and 5904 m/z, which differed most between patients with EM and controls, and identified them as fragments of ATP1B4, and the fibrinogen alpha (FGA) isoform 1/2 of the FGA chain precursor, respectively. ClinProt can identify EM biomarkers, which – most notably – distinguish even early-stage or minimal disease. We found 5 stable peaks at 4210, 5264, 2660, 5635, and 5904 Da as potential EM biomarkers, the strongest of which were associated with ATP1B4 (4210 Da) and FGA (5904 Da); this indicates that ATP1B4 and FGA are associated with EM pathogenesis.