Metabolomic study of human tissue and urine in clear cell renal carcinoma by LC-HRMS and PLS-DA

Abstract

Renal cell carcinoma (RCC) is the most prevalent and lethal malignancy of the kidney. Despite all the efforts made, no tissue biomarker is currently used in the clinical management of patients with kidney cancer. A search for possible biomarkers in urine for clear cell renal cell carcinoma (ccRCC) has been conducted. Non-targeted metabolomic analyses were performed on paired samples of surgically removed renal cancer and normal tissue, as well as on urine samples. Extracts were analyzed by liquid chromatography/high-resolution mass spectrometry (LC-HRMS). Hydroxybutyrylcarnitine, decanoylcarnitine, propanoylcarnitine, carnitine, dodecanoylcarnitine, and norepinephrine sulfate were found in much higher concentrations in both cancer tissues (compared with the paired normal tissue) and in urine of cancer patients (compared with control urine). In contrast, riboflavin and acetylaspartylglutamate (NAAG) were present at significantly higher concentrations both in normal kidney tissue as well as in urine samples of healthy persons. This preliminary study resulted in the identification of several compounds that may be considered potential clear cell renal carcinoma biomarkers. Graphical abstractPLS-DA plot based on LC-MS data for normal and cancer human tissue samples. The aim of this work was the identification of up- and downregulated compounds that could potentially serve as renal cancer biomarkers. Electronic supplementary materialThe online version of this article (10.1007/s00216-018-1059-x) contains supplementary material, which is available to authorized users.

Urinary Metabolomics Validates Metabolic Differentiation Between Renal Cell Carcinoma Stages and Reveals a Unique Metabolic Profile for Oncocytomas

“…Significantly higher urinary carnitine was detected in chromophobes and ccRCC relative to oncocytomas. This finding is particularly interesting as elevated levels of carnitine and its derivatives have been previously reported in the urine of RCC patients and confirmed in xenograft models and RCC cell lines [9,24]. These authors, however, did not define the histological class of the samples involved but revealed a stage-dependent increase of urinary carnitine and acylcarnitines in RCC.…”

“…In addition, we have detected increased o-acetylcarnitine in all RCC stages relative to benign samples (Table 2). Carnitine and acylcarnitines are essential intermediates for the transfer of long chain fatty acids to the mitochondria for β-oxidation and an accumulation in the cell may imply an increased demand as a result of rapid fatty acid oxidation to meet higher tumoral energy requirements [24]. Conversely, Wettersten et al, found that the accumulation of acylcarnitine did not overlap with upregulation of fatty acid oxidation enzymes in RCC [25].…”

Differences in Fecal Microbiomes and Metabolomes of People With vs Without Irritable Bowel Syndrome and Bile Acid Malabsorption

“…They include a number of metabolites of host or bacterial origin including allantoin, and cis-4-decenedioic acid, decanoylcarnitine, and dodecanedioylcarnitine, respectively. These metabolites and compounds are indicative of urea metabolism 42 and fatty acid oxidation defects associated with disease, 43 which may be relevant for IBS pathology. However, as noted, the strongest features that separate the IBS urine metabolome (Supplementary Table 15) are associated with the metabolism of dietary or medication components (nodes E5 and E7).…”

LC-MS based metabolomic profiling for renal cell carcinoma histologic subtypes

“…In the last decade, untargeted metabolomic profiling, using liquid chromatography combined with mass spectrometry (LC-MS), has proven to be a promising tool in kidney cancer diagnostics and research. Previous MS-based metabolomic studies have already shown the possibility of discriminate RCC patients from healthy controls using tissue 14–19 , urine 17,20–22 or serum 23 . Moreover, a recent study has also demonstrated the possibility of discrimination of different RCC stages, from 1 to 4, using combined metabolomic studies 24 .…”