Abstract
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.
Highlights
Renal cell carcinoma (RCC) accounts for more than 90% of all kidney malignancies [1] and represents the second most lethal urological cancer [2]
We further investigated which metabolites might discriminate renal cell carcinoma (RCC) cell lines according to their histological subtype and metastatic potential
The two most common histological subtypes, clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC), at different disease stages were selected for this study, extending our investigation to the metabolic differences that characterize the histological subtype and tumor stage
Summary
Renal cell carcinoma (RCC) accounts for more than 90% of all kidney malignancies [1] and represents the second most lethal urological cancer [2]. Comprising a heterogeneous group of tumors, RCC can be subdivided into several histological subtypes according to distinct clinical and histological features and different outcomes [3,4]. RCC has a favorable prognosis when detected at an early stage [7]. This disease prevails asymptomatically until the advanced stages [8] and no satisfactory biomarkers for clinical management are currently used [9,10]. The development of accurate and non-invasive diagnostic methods based on detection of specific biomarkers in an early stage is of upmost relevance for RCC prognosis and follow-up [9,10]
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