Head-to-Head Comparison and Evaluation of 92 Plasma Protein Biomarkers for Early Detection of Colorectal Cancer in a True Screening Setting
Head-to-Head Comparison and Evaluation of 92 Plasma Protein Biomarkers for Early Detection of Colorectal Cancer in a True Screening Setting
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DOI：
10.1158/1078-0432.ccr-14-3051
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发表时间：
2015-07-15
影响因子：
11.5
通讯作者：
Brenner, Hermann
中科院分区：
文献类型：
--
作者：
Chen, Hongda;Zucknick, Manuela;Brenner, Hermann
目的：新的无创性基于血液的筛查测试是非常需要的早期发现结直肠癌。我们的目的是对92种基于血浆的肿瘤相关蛋白生物标志物的诊断性能进行头对头比较，以在真正的筛查环境中早期检测结直肠癌。在2005-2012年在筛查结肠镜检查参与者队列中招募的所有可用的35名结直肠癌携带者和54名无结直肠肿瘤的男性和女性的代表性样本中（N = 5，516），测量92种蛋白质生物标志物的血浆水平。进行ROC分析以评价诊断性能。通过Lasso逻辑回归模型开发了多标记算法，并在独立验证集中进行了验证。632（+）bootstrap方法被用来调整潜在的高估诊断performance.Results：17个蛋白质标记物被确定为大肠癌病例和对照组之间的血浆水平显示统计学显着差异。这17个个体标志物的ROC曲线下面积（AUC）的调整范围为0.55至0.70。构建了八标记分类器，将调整后的AUC增加至0.77 [95%置信区间（CI），0.59-0.91]。当在独立验证集中验证该算法时，AUC为0.76（95%CI，0.65-0.85），在临界水平产生80%和90%特异性的敏感性为65%（95% CI，41-80%）和44%（95% CI，24-72%）。确定的蛋白质生物标志物谱可能有助于开发一种用于早期检测结直肠癌的强大的多标志物血液检测。(C)2015年AACR。
Purpose: Novel noninvasive blood-based screening tests are strongly desirable for early detection of colorectal cancer. We aimed to conduct a head-to-head comparison of the diagnostic performance of 92 plasma-based tumor-associated protein biomarkers for early detection of colorectal cancer in a true screening setting.Experimental Design: Among all available 35 carriers of colorectal cancer and a representative sample of 54 men and women free of colorectal neoplasms recruited in a cohort of screening colonoscopy participants in 2005-2012 (N = 5,516), the plasma levels of 92 protein biomarkers were measured. ROC analyses were conducted to evaluate the diagnostic performance. A multi-marker algorithm was developed through the Lasso logistic regression model and validated in an independent validation set. The .632(+) bootstrap method was used to adjust for the potential overestimation of diagnostic performance.Results: Seventeen protein markers were identified to show statistically significant differences in plasma levels between colorectal cancer cases and controls. The adjusted area under the ROC curves (AUC) of these 17 individual markers ranged from 0.55 to 0.70. An eight-marker classifier was constructed that increased the adjusted AUC to 0.77 [95% confidence interval (CI), 0.59-0.91]. When validating this algorithm in an independent validation set, the AUC was 0.76 (95% CI, 0.65-0.85), and sensitivities at cutoff levels yielding 80% and 90% specificities were 65% (95% CI, 41-80%) and 44% (95% CI, 24-72%), respectively.Conclusions: The identified profile of protein biomarkers could contribute to the development of a powerful multimarker blood-based test for early detection of colorectal cancer. (C) 2015 AACR.