Renal cell carcinoma (RCC) accounts for several percent of all adult malignant tumor cases and is directly associated with over 120 thousand death cases worldwide annually. Therefore, there is a need for cancer biomarker tests and methods capable of discriminating between normal and malignant tissue. It is demonstrated that gold nanoparticle enhanced target (AuNPET), a nanoparticle-based, surface-assisted laser desorption/ionization (SALDI)-type mass spectrometric method for analysis and imaging, can differentiate between normal and cancerous renal tissue. Diglyceride DG(18:1/20:0)-sodium adduct and protonated octadecanamide ions were found to have greatly elevated intensities in cancerous part of analyzed tissue specimen. Compounds responsible for mentioned ions formation were pointed out as a potential clear cell RCC biomarkers. Their biological properties and localization on the tissue surface are also discussed. Potential application of presented results may also facilitate clinical decision making during surgery for large renal masses.
Infrared (IR) laser ablation-remote-electrospray ionization (LARESI) platform coupled to a tandem mass spectrometer (MS/MS) operated in selected reaction monitoring (SRM) or multiple reaction monitoring (MRM) modes was developed and employed for imaging of target metabolites in human kidney cancer tissue. SRM or MRM modes were employed to avoid artifacts that are present in full scan MS mode. Four tissue samples containing both cancerous and noncancerous regions, obtained from three patients with renal cell carcinoma (RCC), were imaged. Sixteen endogenous metabolites that were reported in the literature as varying in abundance between cancerous and noncancerous areas in various human tissues were selected for analysis. Target metabolites comprised ten amino acids, four nucleosides and nucleobases, lactate, and vitamin E. For comparison purposes, images of the same metabolites were obtained with ultraviolet (UV) desorption/ionization mass spectrometry imaging (UV-LDI-MSI) using monoisotopic silver-109 nanoparticle-enhanced target ( 109 AgNPET) in full-scan MS mode. The acquired MS images revealed differences in abundances of selected metabolites between cancerous and noncancerous regions of the kidney tissue. Importantly, the two imaging methods offered similar results. This study demonstrates the applicability of the novel ambient LARESI SRM/MRM MSI method to both investigating and discovering cancer biomarkers in human tissue.
Kidney cancer is one of the most frequently diagnosed and the most lethal urinary cancer. Despite all the efforts made, no serum-specific biomarker is currently used in the clinical management of patients with this tumor. In this study, comprehensive high-resolution proton nuclear magnetic resonance spectroscopy ( 1 H NMR) and silver-109 nanoparticle-enhanced steel target laser desorption/ionization mass spectrometry ( 109 AgNPET LDI MS) approaches were conducted, in conjunction with multivariate data analysis, to discriminate the global serum metabolic profiles of kidney cancer ( n = 50) and healthy volunteers ( n = 49). Eight potential biomarkers have been identified using 1 H NMR metabolomics and nine mass spectral features which differed significantly ( p < 0.05) between kidney cancer patients and healthy volunteers, as observed by LDI MS. A partial least squares discriminant analysis (OPLS-DA) model generated from metabolic profiles obtained by both analytical approaches could robustly discriminate normal from cancerous samples (Q 2 > 0.7), area under the receiver operative characteristic curve (ROC) AUC > 0.96. Compared with healthy human serum, kidney cancer serum had higher levels of glucose and lower levels of choline, glycerol, glycine, lactate, leucine, myo -inositol, and 1-methylhistidine. Analysis of differences between these metabolite levels in patients with different types and grades of kidney cancer was undertaken. Our results, derived from the combination of LDI MS and 1 H NMR methods, suggest that serum biomarkers identified herein appeared to have great potential for use in clinical prognosis and/or diagnosis of kidney cancer. Graphical abstract Electronic supplementary material The online version of this article (10.1007/s00216-020-02807-1) contains supplementary material, which is available to authorized users.
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.
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