Application of Bayesian modeling of autologous antibody responses against ovarian tumor-associated antigens to cancer detection
Application of Bayesian modeling of autologous antibody responses against ovarian tumor-associated antigens to cancer detection
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DOI：
10.1158/0008-5472.can-05-0669
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发表时间：
2006-02-01
期刊：
影响因子：
11.2
通讯作者：
Roden, RBS
中科院分区：
文献类型：
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作者：
Erkanli, A;Taylor, DD;Roden, RBS
上皮性卵巢癌(EOC)的早期检测迫切需要生物标志物。患者可以产生抗肿瘤相关抗原(TAA)的抗体。我们测试了候选卵巢TAA抗体的多重检测和统计建模以区分EOC患者和对照组的血清。同时检测卵巢早熟妇女或健康对照妇女的血清抗体与TAA包被微球的结合。使用马尔科夫链蒙特卡罗计算的贝叶斯模型/变量选择方法被应用于这些数据和血清CA125值，以确定最好的预测模型。对所选模型进行受试者-操作者曲线下面积(AUC)分析。使用针对P53、NY-CO-8和HOXB7的抗体，最佳模型产生的AUC为0.86[95%可信区间(95%CI)，0.78-0.90]来区分EOC患者和健康患者的血清。模型中包含CA125的AUC为0.89(95%氯，0.84-0.92)，而单独使用CA125的AUC为0.83(95%氯，0.81-0.85)。然而，仅用TAA反应，该模型区分了非恶性妇科疾病妇女和晚期或早期卵巢癌患者的独立血清，其AUC分别为0.71(95%CI，0.67-0.76)和0.70(95%CI，0.48-0.75)。血清抗P53、HOXB7抗体与卵巢癌呈正相关，而抗NY-CO-S抗体与卵巢癌呈负相关。这些TAA特异性血清抗体反应的贝叶斯模型显示出早期和晚期卵巢癌患者与非恶性妇科疾病患者的相似区别，并可能是对CA125的补充。
Biomarkers for early detection of epithelial ovarian cancer (EOC) are urgently needed. Patients can generate antibodies to tumor-associated antigens (TAAs). We tested multiplex detection of antibodies to candidate ovarian TAAs and statistical modeling for discrimination of sera of EOC patients and controls. Binding of serum antibody of women with EOC or healthy controls to candidate TAA-coated microspheres was assayed in parallel. A Bayesian model/variable selection approach using Markov Chain Monte Carlo computations was applied to these data, and serum CA125 values, to determine the best predictive model. The selected model was subjected to area under the receiver-operator curve (AUC) analysis. The best model generated an AUC of 0.86 [95% confidence interval (95% CI), 0.78-0.90] for discrimination between sera of EOC patients and healthy patients using antibody specific to p53, NY-CO-8, and HOXB7. Inclusion of CA125 in the model provided an AUC of 0.89 (95% Cl, 0.84-0.92) compared with an AUC of 0.83 (95% Cl, 0.81-0.85) using CA125 alone. However, using TAA responses alone, the model discriminated between independent sera of women with nonmalignant gynecologic conditions and those with advanced-stage or early-stage EOC with AUCs of 0.71 (95% Cl, 0.67-0.76) and 0.70 (95% Cl, 0.48-0.75), respectively. Serum antibody to p53 and HOXB7 is positively associated with EOC, whereas NY-CO-S-specific antibody shows negative association. Bayesian modeling of these TAA-specific serum antibody responses exhibits similar discrimination of patients with early-stage and advanced-stage EOC from women with nonmalignant gynecologic conditions and may be complementary to CA125.