Amaro Filipa, Pinto Joana, Rocha Sílvia, Araújo Ana Margarida, Miranda-Gonçalves Vera, Jerónimo Carmen, Henrique Rui, de Lourdes Bastos Maria, Carvalho Márcia, de Pinho Paula Guedes
UCIBIO, REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
Master in Oncology, Institute of Biomedical Sciences Abel Salazar-University of Porto (ICBAS-UP), 4050-313 Porto, Portugal.
Metabolites. 2020 Apr 27;10(5):174. doi: 10.3390/metabo10050174.
The identification of noninvasive biomarkers able to detect renal cell carcinoma (RCC) at an early stage remains an unmet clinical need. The recognition that altered metabolism is a core hallmark of cancer boosted metabolomic studies focused in the search for cancer biomarkers. The present work aims to evaluate the performance of the volatile metabolites present in the extracellular medium to discriminate RCC cell lines with distinct histological subtypes (clear cell and papillary) and metastatic potential from non-tumorigenic renal cells. Hence, volatile organic compounds (VOCs) and volatile carbonyl compounds (VCCs) were extracted by headspace solid-phase microextraction (HS-SPME) and analyzed by gas chromatography-mass spectrometry (GC-MS). Multivariate and univariate analysis unveiled a panel of metabolites responsible for the separation between groups, mostly belonging to ketones, alcohols, alkanes and aldehydes classes. Some metabolites were found similarly altered for all RCC cell lines compared to non-tumorigenic cells, namely 2-ethylhexanol, tetradecane, formaldehyde, acetone (increased) and cyclohexanone and acetaldehyde (decreased). Furthermore, significantly altered levels of cyclohexanol, decanal, decane, dodecane and 4-methylbenzaldehyde were observed in all metastatic RCC cell lines when compared with the non-metastatic ones. Moreover, some alterations in the volatile composition were also observed between RCC histological subtypes. Overall, our results demonstrate the potential of volatile profiling for identification of noninvasive candidate biomarkers for early RCC diagnosis.
能够在早期检测出肾细胞癌（RCC）的非侵入性生物标志物的鉴定仍然是一项未满足的临床需求。代谢改变是癌症的一个核心特征，这一认识推动了专注于寻找癌症生物标志物的代谢组学研究。本研究旨在评估细胞外培养基中挥发性代谢物的性能，以区分具有不同组织学亚型（透明细胞和乳头状）以及转移潜能的RCC细胞系与非致瘤性肾细胞。因此，通过顶空固相微萃取（HS-SPME）提取挥发性有机化合物（VOCs）和挥发性羰基化合物（VCCs），并采用气相色谱-质谱联用（GC-MS）进行分析。多变量和单变量分析揭示了一组负责区分不同组别的代谢物，它们大多属于酮类、醇类、烷烃类和醛类。与非致瘤性细胞相比，发现所有RCC细胞系的一些代谢物都有类似的变化，即2-乙基己醇、十四烷、甲醛、丙酮（增加）以及环己酮和乙醛（减少）。此外，与非转移性RCC细胞系相比，所有转移性RCC细胞系中均观察到环己醇、癸醛、癸烷、十二烷和4-甲基苯甲醛的水平有显著变化。此外，在RCC组织学亚型之间也观察到挥发性成分的一些改变。总体而言，我们的结果证明了挥发性分析在鉴定早期RCC诊断的非侵入性候选生物标志物方面的潜力。
