Protein and glycomic plasma markers for early detection of adenoma and colon cancer.
Protein and glycomic plasma markers for early detection of adenoma and colon cancer.
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DOI：
10.1136/gutjnl-2016-312794
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发表时间：
2018-03
期刊：
影响因子：
24.5
通讯作者：
Lampe PD
中科院分区：
文献类型：
--
作者：
Rho JH;Ladd JJ;Li CI;Potter JD;Zhang Y;Shelley D;Shibata D;Coppola D;Yamada H;Toyoda H;Tada T;Kumada T;Brenner DE;Hanash SM;Lampe PD
发现并确认基于血液的结肠癌早期检测标志物。我们创建了一个高密度抗体微阵列来检测被诊断为结肠癌的个体在抽血后<3年（即诊断前）和无癌症的匹配对照中血浆蛋白水平的差异。与对照组相比，对诊断为腺瘤或癌症的人的血浆样本进行了潜在标记物测试。通过第三组样本的免疫印迹、第四组大样本的Luminex检测和组织微阵列的免疫组化（IHC）来检测最佳5个标记面板的成分。在诊断前样本中，我们发现78个蛋白显著（t检验）增加，其中32个在诊断样本中得到证实。在此基础上，建立了BAG家族分子伴侣调节因子4 （BAG4）、白细胞介素-6受体亚单位β (IL6ST)、血管性血友病因子（VWF）和CD44或表皮生长因子受体（EGFR）的最佳4个标记面板。每个小组成员和小组也分别通过免疫印迹和Luminex分别在独立的第三和第四组样本中显示诊断性腺瘤和癌症样本的增加。免疫组化结果显示腺瘤和癌组织中BAG4、IL6ST和CD44水平升高。加入EGFR和CD44唾液Lewis-A和-X含量提高了面板性能。蛋白质/糖蛋白面板在结肠癌样本中具有统计学意义上的显著性升高，其特征为AUCs范围分别为0.90 （95% CI, 0.82-0.98）至0.86 (95% CI, 0.83-0.88)，对于较大的第二组和第四组。包括BAG4、IL6ST、VWF、EGFR和CD44蛋白/糖组学在内的一个小组在早期结肠癌的检测中表现良好，应该在更大规模的研究中进一步检查。
To discover and confirm blood-based colon cancer early-detection markers. We created a high-density antibody microarray to detect differences in protein levels in plasma from individuals diagnosed with colon cancer <3 years after blood was drawn (i.e., prediagnostic) and cancer-free, matched controls. Potential markers were tested on plasma samples from people diagnosed with adenoma or cancer, compared to controls. Components of an optimal 5-marker panel were tested via immunoblotting using a third sample set, Luminex assay in a large fourth sample set and immunohistochemistry (IHC) on tissue microarrays. In the prediagnostic samples, we found 78 significantly (t-test) increased proteins, 32 of which were confirmed in the diagnostic samples. From these 32, optimal 4-marker panels of BAG family molecular chaperone regulator 4 (BAG4), interleukin-6 receptor subunit beta (IL6ST), von Willebrand factor (VWF) and CD44 or epidermal growth factor receptor (EGFR) were established. Each panel member and the panels also showed increases in the diagnostic adenoma and cancer samples, in independent third and fourth sample sets via immunoblot and Luminex, respectively. IHC results showed increased levels of BAG4, IL6ST and CD44 in adenoma and cancer tissues. Inclusion of EGFR and CD44 sialyl Lewis-A and –X content increased the panel performance. The protein/glycoprotein panel was statistically significantly higher in colon cancer samples, characterized by a range of AUCs from 0.90 (95% CI, 0.82–0.98) to 0.86 (95% CI, 0.83–0.88), for the larger second and fourth sets, respectively. A panel including BAG4, IL6ST, VWF, EGFR and CD44 protein/glycomics performed well for detection of early stages of colon cancer and should be further examined in larger studies.