Division of Biostatistics, Department of Public Health Sciences, University of California, Davis, California 95616, USA.
OMICS. 2011 May;15(5):293-303. doi: 10.1089/omi.2010.0094. Epub 2011 Feb 24.
Kidney cancer is the seventh most common cancer in the Western world, its incidence is increasing, and it is frequently metastatic at presentation, at which stage patient survival statistics are grim. In addition, there are no useful biofluid markers for this disease, such that diagnosis is dependent on imaging techniques that are not generally used for screening. In the present study, we use metabolomics techniques to identify metabolites in kidney cancer patients' urine, which appear at different levels (when normalized to account for urine volume and concentration) from the same metabolites in nonkidney cancer patients. We found that quinolinate, 4-hydroxybenzoate, and gentisate are differentially expressed at a false discovery rate of 0.26, and these metabolites are involved in common pathways of specific amino acid and energetic metabolism, consistent with high tumor protein breakdown and utilization, and the Warburg effect. When added to four different (three kidney cancer-derived and one "normal") cell lines, several of the significantly altered metabolites, quinolinate, α-ketoglutarate, and gentisate, showed increased or unchanged cell proliferation that was cell line-dependent. Further evaluation of the global metabolomics analysis, as well as confirmation of the specific potential biomarkers using a larger sample size, will lead to new avenues of kidney cancer diagnosis and therapy.
在西方世界，肾癌是第七大常见癌症，其发病率正在上升，且在发病时常常已经转移，此时患者的生存统计数据不容乐观。此外，针对这种疾病，目前还没有有用的生物体液标志物，因此诊断依赖于一般不用于筛查的成像技术。在本研究中，我们使用代谢组学技术来鉴定肾癌患者尿液中的代谢物，这些代谢物的水平与非肾癌患者的相同代谢物（经尿体积和浓度校正后）不同。我们发现喹啉酸、4-羟基苯甲酸和龙胆酸在错误发现率为 0.26 时有差异表达，这些代谢物涉及特定氨基酸和能量代谢的常见途径，与高肿瘤蛋白分解和利用以及沃伯格效应一致。当将几种明显改变的代谢物（喹啉酸、α-酮戊二酸和龙胆酸）添加到四种不同的（三种肾癌衍生和一种“正常”）细胞系中时，这些代谢物显示出依赖于细胞系的细胞增殖增加或不变。对全局代谢组学分析的进一步评估，以及使用更大的样本量对特定潜在生物标志物的确认，将为肾癌的诊断和治疗开辟新途径。
