Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada.
Department of Medicine, University of Alberta, Edmonton, AB, Canada.
Cancer Biomark. 2023;36(1):17-30. doi: 10.3233/CBM-220034.
African colorectal cancer (CRC) rates are rising rapidly. A low-cost CRC screening approach is needed to identify CRC from non-CRC patients who should be sent for colonoscopy (a scarcity in Africa).
To identify urinary metabolite biomarkers that, combined with easy-to-measure clinical variables, would identify patients that should be further screened for CRC by colonoscopy. Ideal metabolites would be water-soluble and easily translated into a sensitive, low-cost point-of-care (POC) test.
Liquid-chromatography mass spectrometry (LC-MS/MS) was used to quantify 142 metabolites in spot urine samples from 514 Nigerian CRC patients and healthy controls. Metabolite concentration data and clinical characteristics were used to determine optimal sets of biomarkers for identifying CRC from non-CRC subjects.
Our statistical analysis identified N1, N12-diacetylspermine, hippurate, p-hydroxyhippurate, and glutamate as the best metabolites to discriminate CRC patients via POC screening. Logistic regression modeling using these metabolites plus clinical data achieved an area under the receiver-operator characteristic (AUCs) curves of 89.2% for the discovery set, and 89.7% for a separate validation set.
Effective urinary biomarkers for CRC screening do exist. These results could be transferred into a simple, POC urinary test for screening CRC patients in Africa.
非洲结直肠癌（CRC）的发病率正在迅速上升。需要一种低成本的 CRC 筛查方法来识别应该接受结肠镜检查的 CRC 患者和非 CRC 患者（在非洲这种检查稀缺）。
确定尿液代谢生物标志物，这些标志物与易于测量的临床变量相结合，可以识别需要进一步接受结肠镜检查筛查 CRC 的患者。理想的代谢物应该是水溶性的，并且易于转化为敏感、低成本的即时检测（POC）测试。
使用液相色谱-质谱联用（LC-MS/MS）定量分析了 514 名尼日利亚 CRC 患者和健康对照者的尿液样本中的 142 种代谢物。代谢物浓度数据和临床特征用于确定用于通过 POC 筛查从非 CRC 受试者中识别 CRC 的最佳生物标志物组合。
我们的统计分析确定 N1、N12-二乙酰精胺、马尿酸、对羟基马尿酸和谷氨酸是通过 POC 筛查区分 CRC 患者的最佳代谢物。使用这些代谢物加上临床数据进行逻辑回归建模，在发现组中的受试者工作特征（ROC）曲线下面积（AUCs）为 89.2%，在独立验证组中的 AUCs 为 89.7%。
CRC 筛查的有效尿液生物标志物确实存在。这些结果可以转化为一种简单的 POC 尿液检测方法，用于筛查非洲的 CRC 患者。
