Validation of urine p-cresol glucuronide as renal cell carcinoma non-invasive biomarker

Description of the study: Renal cell carcinoma (RCC) stands among the most lethal urological malignancies. Most RCCs are incidentally diagnosed as initial symptoms are unspecific. Novel, minimally-invasive diagnostic and prognostic methods for RCC are needed, ideally in urine. Using UPLC-Q-ToF MS untargeted metabolomic analysis in urine, we previously revealed p-cresol glucuronide as potential RCC diagnostic marker. Additionally, urine samples one-year post-nephrectomy revealed isobutyryl-L-carnitine and L-proline betaine as potential RCC prognostic markers. Our present aim was to validate these differences in an independent cohort of RCC patients and healthy controls to strengthen their value as non-invasive biomarkers. In an independent cohort of 69 RCC patients and 52 controls we validated an increase in p-cresol glucuronide in urine from patients at diagnosis compared to controls (P=0.0043). It remained increased one-year post-nephrectomy (P=0.0288). The value of p-cresol glucuronide for RCC diagnosis was assessed with ROC curves analysis (AUC=0.66, 95% Confidence Interval 0.56-0.76). The role of isobutyryl-L-carnitine and L-proline betaine as prognostic markers could not be validated and will require a larger cohort. Our findings confirm the value of p-cresol glucuronide in urine as diagnostic marker for RCC in an independent cohort. This non-invasive method holds promise for enhancing patient care by reducing the need for potentially risky diagnostic procedures. Further metaproteomics-oriented approaches towards the tyrosine oxidation pathway and microbiota metagenomics studies may promote a holistic management of RCC. Description of the data: We provided data in .d format adquired with Agilent.研究概况： 肾细胞癌（Renal cell carcinoma, RCC）是致死率较高的泌尿生殖系统恶性肿瘤之一。由于该疾病初始症状缺乏特异性，多数肾细胞癌患者为偶发确诊。目前亟需开发新型、微创的肾细胞癌诊断与预后评估方法，理想情况下可通过尿液样本实现无创检测。 此前本团队借助超高效液相色谱-四极杆飞行时间质谱（UPLC-Q-ToF MS）的非靶向代谢组学分析技术，对尿液样本进行检测，已筛选出对甲酚葡糖苷酸（p-cresol glucuronide）作为潜在的肾细胞癌诊断标志物。此外，对肾切除术（nephrectomy）一年后的尿液样本分析结果显示，异丁酰-L-肉碱（isobutyryl-L-carnitine）与L-脯氨酸甜菜碱（L-proline betaine）可作为潜在的肾细胞癌预后评估标志物。本研究旨在通过独立的肾细胞癌患者与健康对照队列，验证上述代谢物的差异表达，以进一步证实其作为无创生物标志物的临床价值。 本研究纳入69例肾细胞癌患者与52例健康对照组成的独立队列，验证了确诊时患者尿液中的对甲酚葡糖苷酸水平较健康对照显著升高（P=0.0043），且该指标在肾切除术一年后仍维持较高水平（P=0.0288）。通过受试者工作特征曲线（ROC curves）分析评估对甲酚葡糖苷酸用于肾细胞癌诊断的效能，其曲线下面积（AUC）为0.66，95%置信区间为0.56-0.76。而异丁酰-L-肉碱与L-脯氨酸甜菜碱作为预后评估标志物的结论未能在本队列中得到验证，后续需扩大样本量开展进一步研究。 本研究结果在独立队列中证实了尿液中对甲酚葡糖苷酸作为肾细胞癌诊断标志物的价值。该无创检测方法可减少患者接受潜在风险较高的诊断操作，有望改善临床患者诊疗效果。未来可围绕酪氨酸氧化通路开展宏蛋白质组学相关研究，并结合微生物组宏基因组学分析，以实现肾细胞癌的整体化管理。 数据集说明： 本数据集提供安捷伦（Agilent）平台采集的.d格式原始数据。