School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin 53705, United States.
Department of Oncology, Laboratory of Genetics, University of Wisconsin-Madison, Madison, Wisconsin 53705, United States.
J Proteome Res. 2023 May 5;22(5):1483-1491. doi: 10.1021/acs.jproteome.3c00006. Epub 2023 Apr 4.
A major challenge in reducing the death rate of colorectal cancer is to screen patients using low-invasive testing. A blood test shows a high compliance rate with reduced invasiveness. In this work, a multiplex isobaric tag labeling strategy coupled with mass spectrometry is adopted to relatively quantify primary and secondary amine-containing metabolites in serum for the discovery of metabolite level changes of colorectal cancer. Serum samples from patients at different risk statuses and colorectal cancer growth statuses are studied. Metabolite identification is based on accurate mass matching and/or retention time of labeled metabolite standards. We quantify 40 metabolites across all the serum samples, including 18 metabolites validated with standards. We find significantly decreased levels of threonine and asparagine in the patients with growing adenomas or high-risk adenomas ( < 0.05). Glutamine levels decrease in patients with adenomas of unknown growth status or high-risk adenomas. In contrast, arginine levels are elevated in patients with low-risk adenoma. Receiver operating characteristic analysis shows high sensitivity and specificity of these metabolites for detecting growing adenomas. Based on these results, we conclude that a few metabolites identified here might contribute to distinguishing colorectal patients with growing adenomas from normal individuals and patients with unknown growth status of adenomas.
降低结直肠癌死亡率的一个主要挑战是使用低侵入性检测对患者进行筛查。血液检测具有较高的顺应性和较低的侵入性。在这项工作中，采用了一种多重同位素标记标签结合质谱的方法，相对定量血清中含伯胺和仲胺的代谢物，以发现结直肠癌的代谢物水平变化。研究了不同风险状况和结直肠腺瘤生长状况患者的血清样本。代谢物的鉴定基于标记代谢物标准品的精确质量匹配和/或保留时间。我们对所有血清样本进行了 40 种代谢物的定量，其中包括 18 种用标准品验证的代谢物。我们发现，生长中的腺瘤或高危腺瘤患者（<0.05）的苏氨酸和天冬酰胺水平显著降低。在腺瘤生长状态未知或高危腺瘤患者中，谷氨酰胺水平降低。相比之下，低危腺瘤患者的精氨酸水平升高。受试者工作特征分析表明，这些代谢物对检测生长中的腺瘤具有很高的灵敏度和特异性。基于这些结果，我们得出结论，这里鉴定的一些代谢物可能有助于区分生长中的腺瘤患者与正常个体和腺瘤生长状态未知的患者。
