Identification of biomarkers for ovarian cancer using strong anion-exchange ProteinChips: Potential use in diagnosis and prognosis
Identification of biomarkers for ovarian cancer using strong anion-exchange ProteinChips: Potential use in diagnosis and prognosis
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DOI：
10.1073/pnas.2033602100
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发表时间：
2003-10-14
影响因子：
11.1
通讯作者：
Farias-Eisner, R
中科院分区：
文献类型：
--
作者：
Kozak, KR;Amneus, MW;Farias-Eisner, R
采用表面增强激光解吸/电离飞行时间质谱技术在强阴离子交换表面对卵巢癌患者（109例）、良性肿瘤患者（19例）和健康供者（56例）的184份血清样本进行了分析。单变量和多变量统计分析应用于从140个训练血清样本中获得的蛋白质谱数据，确定了三个生物标志物蛋白质面板。第一个由5个候选蛋白生物标志物组成的小组，被称为筛选生物标志物小组，可有效诊断卵巢良恶性肿瘤[敏感性95.7%，特异性82.6%，准确性89.2%，受试者工作特征（ROC）曲线下面积0.94]。另外两个小组分别由5个和4个候选蛋白质生物标志物组成，可有效区分卵巢良性和恶性肿瘤，因此被称为验证生物标志物小组I（敏感性81.5%，特异性94.9%，准确性88.2%,ROC = 0.94）和验证生物标志物小组II（敏感性72.8%，特异性94.9%，准确性83.9%,ROC = 0.90）。3个卵巢癌生物标志物蛋白面板正确诊断了44个盲法试验样本中的41个：22个卵巢恶性肿瘤中有21个[11个早期卵巢癌（I/II）中有10个，11个晚期卵巢癌（III/IV）中有11个]，6个低恶性肿瘤中有6个，6个良性肿瘤中有5个，10个正常患者样本中有9个。总之，我们发现了三种卵巢癌生物标志物蛋白面板，当它们一起使用时，可以有效地区分健康对照和良性或恶性卵巢肿瘤患者的血清样本。
One hundred eighty-four serum samples from patients with ovarian cancer (n = 109), patients with benign tumors (n = 19), and healthy donors (n = 56) were analyzed on strong anion-exchange surfaces using surf ace-enhanced laser desorption/ionization time-of-flight mass spectrometry technology. Univariate and multivariate statistical analyses applied to protein-profiling data obtained from 140 training serum samples identified three biomarker protein panels. The first panel of five candidate protein biomarkers, termed the screening biomarker panel, effectively diagnosed benign and malignant ovarian neoplasia [95.7% sensitivity, 82.6% specificity, 89.2% accuracy, and receiver operating characteristic (ROC) area under the curve of 0.94]. The other two panels, consisting of five and four candidate protein biomarkers each, effectively distinguished between benign and malignant ovarian neoplasia and were therefore referred to as validation biomarker panel I (81.5% sensitivity, 94.9% specificity, 88.2% accuracy, and ROC = 0.94) and validation biomarker panel II (72.8% sensitivity, 94.9% specificity, 83.9% accuracy, and ROC = 0.90). The three ovarian cancer biomarker protein panels correctly diagnosed 41 of the 44 blinded test samples: 21 of 22 malignant ovarian neoplasias [10 of 11 early-stage ovarian cancer (I/II) and 11 of 11 advanced-stage ovarian cancer (III/IV)], 6 of 6 low malignant potential, 5 of the 6 benign tumors, and 9 of 10 normal patient samples. In conclusion, we have discovered three ovarian cancer biomarker protein panels that, when used together, effectively distinguished serum samples from healthy controls and patients with either benign or malignant ovarian neoplasia.