Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, 11221, Taiwan.
Molecular Medicine Research Center, Chang Gung University, Taoyuan, 33302, Taiwan.
BMC Bioinformatics. 2021 Jun 5;22(1):305. doi: 10.1186/s12859-021-04235-z.
Early detection of bladder cancer remains challenging because patients with early-stage bladder cancer usually have no incentive to take cytology or cystoscopy tests if they are asymptomatic. Our goal is to find non-invasive marker candidates that may help us gain insight into the metabolism of early-stage bladder cancer and be examined in routine health checks.
We acquired urine samples from 124 patients diagnosed with early-stage bladder cancer or hernia (63 cancer patients and 61 controls). In which 100 samples were included in our marker discovery cohort, and the remaining 24 samples were included in our independent test cohort. We obtained metabolic profiles of 922 compounds of the samples by gas chromatography-mass spectrometry. Based on the metabolic profiles of the marker discovery cohort, we selected marker candidates using Wilcoxon rank-sum test with Bonferroni correction and leave-one-out cross-validation; we further excluded compounds detected in less than 60% of the bladder cancer samples. We finally selected eight putative markers. The abundance of all the eight markers in bladder cancer samples was high but extremely low in hernia samples. Moreover, the up-regulation of these markers might be in association with sugars and polyols metabolism.
In the present study, comparative urine metabolomics selected putative metabolite markers for the detection of early-stage bladder cancer. The suggested relations between early-stage bladder cancer and sugars and polyols metabolism may create opportunities for improving the detection of bladder cancer.
膀胱癌的早期检测仍然具有挑战性,因为如果早期膀胱癌患者无症状,他们通常没有动力进行细胞学或膀胱镜检查。我们的目标是找到非侵入性的候选标志物,可以帮助我们深入了解早期膀胱癌的代谢,并在常规健康检查中进行检查。
我们从 124 名被诊断为早期膀胱癌或疝气的患者(63 名癌症患者和 61 名对照)中获得了尿液样本。其中 100 个样本被纳入我们的标志物发现队列,其余 24 个样本被纳入我们的独立测试队列。我们通过气相色谱-质谱法获得了 922 种样本化合物的代谢谱。基于标志物发现队列的代谢谱,我们使用具有 Bonferroni 校正的 Wilcoxon 秩和检验和留一法交叉验证选择标志物候选物;我们进一步排除了在少于 60%的膀胱癌样本中检测到的化合物。我们最终选择了 8 种假定的标志物。在膀胱癌样本中,所有 8 种标志物的丰度都很高,但在疝气样本中却极低。此外,这些标志物的上调可能与糖和多元醇代谢有关。
在本研究中,比较尿液代谢组学选择了用于检测早期膀胱癌的假定代谢标志物。早期膀胱癌与糖和多元醇代谢之间的提示关系可能为提高膀胱癌的检测提供机会。