Identification of urinary biomarkers of colorectal cancer: Towards the development of a colorectal screening test in limited resource settings.
Identification of urinary biomarkers of colorectal cancer: Towards the development of a colorectal screening test in limited resource settings.
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DOI：
10.3233/cbm-220034
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发表时间：
2022-07
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通讯作者：
Lun Zhang;Jiamin Zheng;K. Ismond;Scott MacKay;Marcia A LeVatte;J. Constable;Olusegun Isaac Alatise;T. Peter Kingham;D. Wishart
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文献类型：
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作者：
Lun Zhang;Jiamin Zheng;K. Ismond;Scott MacKay;Marcia A LeVatte;J. Constable;Olusegun Isaac Alatise;T. Peter Kingham;D. Wishart
背景非洲结直肠癌(CRC)的发病率正在迅速上升。需要一种低成本的结直肠癌筛查方法，以从应该送往结肠镜检查的非结直肠癌患者中识别出结直肠癌(这在非洲是稀缺的)。目的确定尿代谢物生物标志物，结合易于测量的临床变量，识别应通过结肠镜进一步筛查结直肠癌的患者。理想的代谢物应该是水溶性的，并且很容易转化为敏感的、低成本的护理点(POC)测试。方法采用液-质联用技术(LC-MS/MS)对514例尼日利亚结直肠癌患者和514例健康对照的尿样中142种代谢物进行定量分析。代谢物浓度数据和临床特征被用来确定从非结直肠癌受试者中识别结直肠癌的最佳生物标志物集合。结果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筛查区分结直肠癌患者的最佳代谢物。使用这些代谢物和临床数据进行Logistic回归建模，发现集的接受者-操作员特征(AUCS)曲线下的面积为89.2%，单独验证集的面积为89.7%。结论确实存在用于结直肠癌筛查的有效尿液生物标志物。这些结果可以被转移到一种简单的POC尿液测试中，用于在非洲筛查CRC患者。
BACKGROUND 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). OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.