Leman Eddy S, Schoen Robert E, Magheli Ahmed, Sokoll Lori J, Chan Daniel W, Getzenberg Robert H
The Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Clin Cancer Res. 2008 Mar 1;14(5):1349-54. doi: 10.1158/1078-0432.CCR-07-4110.
A blood test to detect colon cancer at a preventable stage would represent a major advancement. We have previously identified colon cancer-specific markers using focused proteomics analysis of nuclear structural proteins. Two of these markers, colon cancer-specific antigen (CCSA)-3 and CCSA-4, have been developed into blood-based markers that are able to distinguish individuals with colorectal cancer from those without. CCSA-2 is a distinct novel colon cancer marker identified using focused proteomics.
Using an indirect ELISA on serum samples obtained from two institutions, we evaluated CCSA-2 as a serum-based colon cancer marker. A total of 111 serum samples from individuals who underwent colonoscopy and were subsequently diagnosed as either being normal or having hyperplastic polyps, nonadvanced adenomas, advanced adenomas, and colorectal cancer were evaluated. A diverse control population that consisted of 125 serum samples was also included in this study.
Receiver operating characteristic analyses were used to measure the sensitivity and specificity of CCSA-2. CCSA-2 at a cutoff of 10.8 mug/mL has overall specificity of 78.4% [95% confidence interval (95% CI), 67.3-87.1%] and sensitivity of 97.3% (95% CI, 85.8-99.5%) in separating individuals with advanced adenomas and colorectal cancer from normal, hyperplastic, and nonadvanced adenoma populations. The receiver operating characteristic curve for CCSA-2 has an area under the curve of 0.90 (95% CI, 0.83-0.95).
Our initial study shows that CCSA-2 is a potential serum-based marker for colon cancer detection with high sensitivity and specificity.
一种能在可预防阶段检测结肠癌的血液检测方法将是一项重大进展。我们之前通过对核结构蛋白进行聚焦蛋白质组学分析，鉴定出了结肠癌特异性标志物。其中两种标志物，即结肠癌特异性抗原（CCSA）-3和CCSA-4，已被开发成基于血液的标志物，能够区分结直肠癌患者和非患者。CCSA-2是通过聚焦蛋白质组学鉴定出的一种独特的新型结肠癌标志物。
我们使用间接酶联免疫吸附测定法（ELISA）对从两个机构获得的血清样本进行检测，以评估CCSA-2作为基于血清的结肠癌标志物。共评估了111份来自接受结肠镜检查并随后被诊断为正常、增生性息肉、非进展性腺瘤、进展性腺瘤和结直肠癌患者的血清样本。本研究还纳入了由125份血清样本组成的多样化对照人群。
采用受试者工作特征分析来衡量CCSA-2的敏感性和特异性。在将进展性腺瘤和结直肠癌患者与正常、增生性和非进展性腺瘤人群区分开时，CCSA-2的临界值为10.8μg/mL，总体特异性为78.4%[95%置信区间（95%CI），67.3 - 87.1%]，敏感性为97.3%（95%CI，85.8 - 99.5%）。CCSA-2的受试者工作特征曲线下面积为0.90（95%CI，0.83 - 0.95）。
我们的初步研究表明，CCSA-2是一种具有高敏感性和特异性的潜在的基于血清的结肠癌检测标志物。
