Increased plasma levels of the APC-interacting protein MAPRE1, LRG1, and IGFBP2 preceding a diagnosis of colorectal cancer in women.
Increased plasma levels of the APC-interacting protein MAPRE1, LRG1, and IGFBP2 preceding a diagnosis of colorectal cancer in women.
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DOI：
10.1158/1940-6207.capr-11-0412
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Hanash SM
中科院分区：
文献类型：
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作者：
Ladd JJ;Busald T;Johnson MM;Zhang Q;Pitteri SJ;Wang H;Brenner DE;Lampe PD;Kucherlapati R;Feng Z;Prentice RL;Hanash SM
队列研究的纵向血液收集提供了在临床诊断之前寻找与疾病相关的蛋白质的方法。我们研究了来自妇女健康倡议（WHI）队列的血浆样本，以确定随后诊断为结直肠癌（CRC）的受试者与在随访期间保持无癌的匹配对照之间血浆蛋白的定量差异。在诊断CRC之前收集的WHI样品的蛋白质组学分析导致鉴定出与对照相比在病例中具有显著（p <0.05）升高的浓度的六种蛋白质。对两种结直肠癌细胞系的蛋白质组学分析显示，6种蛋白质中有5种是由癌细胞产生的。在58对新诊断的CRC样品和对照中，通过酶联免疫吸附测定（ELISA）分别测定MAPRE1、IGFBP2、LRG1和CEA，并且相对于对照，在病例中产生显著升高（p <0.05）。这四种标志物的组合导致ROC具有AUC=0.841和57%的灵敏度和95%的特异性。在诊断前7个月内从病例和匹配对照中收集的一组独立的WHI样本中测试了该组合规则，结果灵敏度为41%，特异性为95%。由CEA、MAPRE1、IGFBP2和LRG1组成的组在诊断前结直肠癌血浆中具有预测价值。
Longitudinal blood collections from cohort studies provide the means to search for proteins associated with disease prior to clinical diagnosis. We investigated plasma samples from the Women’s Health Initiative (WHI) cohort to determine quantitative differences in plasma proteins between subjects subsequently diagnosed with colorectal cancer (CRC) and matched controls that remained cancer free during the period of follow-up. Proteomic analysis of WHI samples collected prior to diagnosis of CRC resulted in the identification of six proteins with significantly (p <0.05) elevated concentrations in cases compared to controls. Proteomic analysis of two colorectal cancer cell lines showed 5 of the 6 proteins were produced by cancer cells. MAPRE1, IGFBP2, LRG1 and CEA were individually assayed by enzyme linked immunosorbent assay (ELISA) in 58 pairs of newly diagnosed CRC samples and controls and yielded significant elevations (p <0.05) among cases relative to controls. A combination of these four markers resulted in an ROC with an AUC=0.841 and 57% sensitivity at 95% specificity. This combination rule was tested in an independent set of WHI samples collected within 7 months prior to diagnosis from cases and matched controls resulting in 41% sensitivity at 95% specificity. A panel consisting of CEA, MAPRE1, IGFBP2 and LRG1 has predictive value in pre-diagnostic colorectal cancer plasmas.