UCIBIO/REQUIMTE, Department of Biological Sciences, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
Cancer Biology & Epigenetics Group-Research Centre, Portuguese Oncology Institute of Porto (CI-IPOP), 4200-072 Porto, Portugal.
J Proteome Res. 2021 Jun 4;20(6):3068-3077. doi: 10.1021/acs.jproteome.0c00936. Epub 2021 Apr 2.
Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer usually associated with asymptomatic development and risk of systemic progression. Hence, reliable molecular biomarkers of ccRCC are needed to provide early and minimally invasive detection. In this study, urinary volatilome profiling of patients diagnosed with ccRCC ( = 75), and cancer-free controls ( = 75), was performed to investigate the presence of a volatile signature characteristic of ccRCC. Volatile organic compounds (VOCs) in general, and more specifically volatile carbonyl compounds (VCCs), present in urine were extracted by headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS). Supervised multivariate models showed a good discriminatory power of ccRCC patients from controls in urine. Overall, 22 volatile metabolites were found significantly altered between the two groups, including aldehydes, ketones, aromatic hydrocarbons, and terpenoids. A candidate six-biomarker panel, comprising octanal, 3-methylbutanal, benzaldehyde, 2-furaldehyde, 4-heptanone, and -cresol, depicted the best performance for ccRCC detection with 83% sensitivity, 79% specificity, and 81% accuracy. Moreover, the ccRCC urinary volatilome signature suggested dysregulation of energy metabolism and overexpression of enzymes associated with carcinogenesis. These findings provide the molecular basis for the fine-tuning of gas-sensing materials for application in the development of a bioelectronic sensor.
透明细胞肾细胞癌 (ccRCC) 是最常见的肾癌类型，通常与无症状发展和全身进展风险相关。因此，需要可靠的 ccRCC 分子生物标志物来提供早期和微创检测。在这项研究中，对诊断为 ccRCC 的患者（n = 75）和无癌症对照（n = 75）的尿液挥发物谱进行了分析，以研究是否存在 ccRCC 特征性的挥发性特征。通过顶空固相微萃取与气相色谱-质谱联用（HS-SPME-GC-MS）提取尿液中一般挥发性有机化合物（VOCs），特别是挥发性羰基化合物（VCCs）。有监督的多变量模型显示，ccRCC 患者与对照组在尿液中的区分能力良好。总体而言，在两组之间发现了 22 种挥发性代谢物发生了明显变化，包括醛、酮、芳烃和萜类化合物。由辛醛、3-甲基丁醛、苯甲醛、2-糠醛、4-庚酮和间甲酚组成的候选六标志物面板，对 ccRCC 检测具有最佳性能，灵敏度为 83%，特异性为 79%，准确性为 81%。此外，ccRCC 尿液挥发物特征提示能量代谢失调和与致癌作用相关的酶过表达。这些发现为精细调整气敏材料以应用于生物电子传感器的开发提供了分子基础。
