Declining plasma fibrinogen alpha fragment identifies HER2-positive breast cancer patients and reverts to normal levels after surgery
Declining plasma fibrinogen alpha fragment identifies HER2-positive breast cancer patients and reverts to normal levels after surgery
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DOI：
10.1021/pr060099u
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发表时间：
2006-11-03
影响因子：
4.4
通讯作者：
Miron, Alexander
中科院分区：
文献类型：
--
作者：
Shi, Qian;Harris, Lyndsay N.;Miron, Alexander
乳腺癌是影响女性的最常见的非皮肤恶性肿瘤。目前，还没有简单的、基于血液的诊断测试来补充放射学筛查并提高检测的灵敏度。为了筛选血浆样本并确定检测HER2阳性乳腺癌的生物标记物，使用了自动机器人样本处理和表面增强激光解吸电离飞行时间质谱仪(SELDI-TOF)。多种统计算法被用来选择区分癌症患者和对照组的生物标记物，产生的平均CV比率从20%到29%不等。在一个独立的测试数据集上验证了一组七个生物标志物，获得了19.1%的最佳错误率。排列测试表明，CV误差的p值小于0.002。此外，使用这些生物标志物的ROC曲线在独立的测试数据集上获得了0.95的曲线下面积值。负责大部分分辨率的标记被鉴定为包含605-629残基的纤维蛋白原α(FGA)片段。与对照组相比，该标志物在癌症患者中的水平较低。这一生物标志物的重要性在一项比较手术前后水平的纵向研究中得到了验证，并在手术后恢复到正常水平。该片段可作为有用的诊断和治疗监测标记物。
Breast cancer is the most common nonskin malignancy affecting women. Currently, no simple, blood-based diagnostic test exists to complement radiological screening and increase sensitivity of detection. To screen plasma specimens and identify biomarkers that detect HER2-positive breast cancer, automated robotic sample processing followed by surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF) mass spectroscopy was used. Multiple statistical algorithms were used to select biomarkers that segregate cancer patients versus controls and produced average CV rates ranging from 20% to 29%. A set of seven biomarkers were validated on an independent test data set and achieved the best error rate of 19.1%. A permutation test indicateded a p-value for CV error less than 0.002. Moreover, a ROC curve using these biomarkers achieved an area-under-the-curve value of 0.95 on an independent test data set. The marker responsible for most of the resolving power was identified as a fragment of Fibrinogen Alpha (FGA) encompassing residues 605-629. This marker was present at lower levels in cancer patients as compared to controls. The importance of this biomarker was validated in a longitudinal study comparing pre- and post-operative levels and was shown to revert to normal levels after surgery. This fragment may serve as a useful diagnostic and treatment-monitoring marker.