DiagNodus Ltd, Babraham Research Campus, Cambridge.
Department of Gastroenterology, St George's Hospital, London, UK.
Eur J Gastroenterol Hepatol. 2019 Oct;31(10):1220-1227. doi: 10.1097/MEG.0000000000001535.
Noninvasive colorectal cancer detection and screening remain global diagnostic challenges because the existing stool tests either lack sensitivity or are complex and expensive. Moreover, colorectal cancer screening uptake is low due to stool sampling inconvenience. We have developed a simple and patient-friendly noninvasive technique for collecting highly informative colorectal mucus. In this study, we aimed to comparatively assess a range of candidate biomarkers in colorectal mucus samples for colorectal cancer detection.
The study included 17 patients with colorectal cancer and 35 healthy controls, who provided noninvasively collected colorectal mucus samples. Protein biomarker quantification in these samples by enzyme-linked immunosorbent assays allowed comparing diagnostic performances of 24 candidate biomarkers that comprised haemoglobin, D-dimer, M2-pyruvate kinase, carcinoembryonic antigen, C-reactive protein, calprotectin, eosinophil-derived neurotoxin, protein S100A12, tumour necrosis factor α, clusterin, soluble cytokeratin 18, caspase-cleaved cytokeratin 18, citrullinated histone H3, peptidyl arginine deiminase 4, epidermal growth factor, epidermal growth factor receptor, matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 1, periostin, vascular endothelial growth factor A, vascular endothelial growth factor receptor 1, vascular cell adhesion molecule 1, intercellular adhesion molecule 1 and mucin 2. Tested biomarkers were ranked for colorectal cancer detection efficiency using receiver operating characteristic curve analysis.
High area under the curve values between 0.943 and 0.768 were observed for haemoglobin, tissue inhibitor of metalloproteinase 1, M2-pyruvate kinase, peptidyl arginine deiminase 4, C-reactive protein, matrix metalloproteinase 9, epidermal growth factor receptor, eosinophil-derived neurotoxin and calprotectin.
Quantification of protein biomarkers in noninvasively collected samples of colorectal mucus certainly allows detecting colorectal cancer. Further clinical evaluation of the optimal biomarkers identified by this study is needed.
非侵入性结直肠癌检测和筛查仍然是全球性的诊断挑战，因为现有的粪便检测要么缺乏敏感性，要么复杂且昂贵。此外，由于粪便采样不便，结直肠癌筛查的参与率很低。我们已经开发出一种简单且患者友好的非侵入性技术，用于收集高度信息丰富的结直肠粘液。在这项研究中，我们旨在比较评估结直肠粘液样本中一系列候选生物标志物在结直肠癌检测中的应用。
该研究纳入了 17 名结直肠癌患者和 35 名健康对照者，他们提供了非侵入性采集的结直肠粘液样本。通过酶联免疫吸附试验定量检测这些样本中的蛋白质生物标志物，比较了 24 种候选生物标志物的诊断性能，这些标志物包括血红蛋白、D-二聚体、M2-丙酮酸激酶、癌胚抗原、C 反应蛋白、钙卫蛋白、嗜酸性粒细胞衍生的神经毒素、S100A12 蛋白、肿瘤坏死因子 α、聚集素、可溶性细胞角蛋白 18、半胱氨酸蛋白酶-cleaved 细胞角蛋白 18、瓜氨酸化组蛋白 H3、肽基精氨酸脱亚氨酶 4、表皮生长因子、表皮生长因子受体、基质金属蛋白酶 9、金属蛋白酶组织抑制剂 1、骨膜蛋白、血管内皮生长因子 A、血管内皮生长因子受体 1、血管细胞黏附分子 1、细胞间黏附分子 1 和粘蛋白 2。使用受试者工作特征曲线分析对候选生物标志物进行了检测效率的排名。
血红蛋白、基质金属蛋白酶 1、M2-丙酮酸激酶、肽基精氨酸脱亚氨酶 4、C 反应蛋白、基质金属蛋白酶 9、表皮生长因子受体、嗜酸性粒细胞衍生的神经毒素和钙卫蛋白的曲线下面积值在 0.943 到 0.768 之间较高。
定量检测非侵入性采集的结直肠粘液样本中的蛋白质生物标志物确实可以检测结直肠癌。需要进一步临床评估本研究确定的最佳生物标志物。
