Multiplex screening of 275 plasma protein biomarkers to identify a signature for early detection of colorectal cancer
Multiplex screening of 275 plasma protein biomarkers to identify a signature for early detection of colorectal cancer
复制标题
DOI：
10.1002/1878-0261.12591
复制
发表时间：
2019-11-13
影响因子：
6.6
通讯作者：
Brenner, Hermann
中科院分区：
文献类型：
--
作者：
Bhardwaj, Megha;Weigl, Korbinian;Brenner, Hermann
基于血液的蛋白质生物标志物可能是结直肠癌（CRC）早期检测的一个有吸引力的选择。在这里，我们使用两阶段设计，通过邻近延伸测定（PEA）测量275种蛋白质标志物，首先在发现集的血浆样本中，该发现集由98例新诊断的CRC病例和100例年龄和性别匹配的对照组组成，在筛查结肠镜检查时无肿瘤。通过最小绝对收缩和使用.632+ bootstrap方法的选择算子回归推导出预测早期或晚期CRC存在的算法，然后在由筛查结肠镜检查伴和不伴CRC的参与者组成的独立验证集中再次使用PEA验证该算法（分别为n = 56和102）。在发现集中获得了由9、12和11种蛋白质标记物组成的所有、早期和晚期CRC的三种不同特征，在0.632 + bootstrap调整后的曲线下面积（AUC）分别为0.92、0.91和0.96。在筛查性结肠镜检查参与者中进行外部验证，得出所有、早期和晚期CRC的AUC分别为0.76 [95%置信区间（95% CI），0.67-0.84]、0.75（95% CI，0.62-0.87）和0.80（95% CI，0.68-0.89）。虽然鉴定的蛋白质标记物与最好的粪便检测没有竞争力，但这些蛋白质可能有助于开发未来用于CRC早期检测的强大血液检测。
Blood-based protein biomarkers may be an attractive option for early detection of colorectal cancer (CRC). Here, we used a two-stage design to measure 275 protein markers by proximity extension assay (PEA), first in plasma samples of a discovery set consisting of 98 newly diagnosed CRC cases and 100 age- and gender-matched controls free of neoplasm at screening colonoscopy. An algorithm predicting the presence of early- or late-stage CRC was derived by least absolute shrinkage and selection operator regression with .632+ bootstrap method, and the algorithms were then validated using PEA again in an independent validation set consisting of participants of screening colonoscopy with and without CRC (n = 56 and 102, respectively). Three different signatures for all-, early-, and late-stage CRC consisting of 9, 12, and 11 protein markers were obtained in the discovery set with areas under the curves (AUCs) after .632 + bootstrap adjustment of 0.92, 0.91, and 0.96, respectively. External validation among participants of screening colonoscopy yielded AUCs of 0.76 [95% confidence interval (95% CI), 0.67-0.84], 0.75 (95% CI, 0.62-0.87), and 0.80 (95% CI, 0.68-0.89) for all-, early-, and late-stage CRC, respectively. Although the identified protein markers are not competitive with the best available stool tests, these proteins may contribute to the development of powerful blood-based tests for CRC early detection in the future.