title: Comprehensive Metabolomic and Lipidomic Profiling of Human Kidney Tissue: A Platform Comparison.
abstract: Metabolite profiling of tissue samples is a promising approach for the characterization of cancer pathways and tumor classification based on metabolic features. Here, we present an analytical method for nontargeted metabolomics of kidney tissue. Capitalizing on different chemical properties of metabolites allowed us to extract a broad range of molecules covering small polar molecules and less polar lipid classes that were analyzed by LC-QTOF-MS after HILIC and RP chromatographic separation, respectively. More than 1000 features could be reproducibly extracted and analyzed (CV < 30%) in porcine and human kidney tissue, which were used as surrogate matrices for method development. To further assess assay performance, cross-validation of the nontargeted metabolomics platform to a targeted metabolomics approach was carried out. Strikingly, from 102 metabolites that could be detected on both platforms, the majority (>90%) revealed Spearman's correlation coefficients ≥0.3, indicating that quantitative results from the nontargeted assay are largely comparable to data derived from classical targeted assays. Finally, as proof of concept, the method was applied to human kidney tissue where a clear differentiation between kidney cancer and nontumorous material could be demonstrated on the basis of unsupervised statistical analysis.
authors.affiliation: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology , 70376 Stuttgart, Germany.|University of Tübingen , 72074 Tübingen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Leuthold
authors.affiliation: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology , 70376 Stuttgart, Germany.|University of Tübingen , 72074 Tübingen, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Schaeffeler
authors.affiliation: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology , 70376 Stuttgart, Germany.|University of Tübingen , 72074 Tübingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Winter
authors.affiliation: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology , 70376 Stuttgart, Germany.|University of Tübingen , 72074 Tübingen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Büttner
authors.affiliation: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology , 70376 Stuttgart, Germany.|University of Tübingen , 72074 Tübingen, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Hofmann
authors.affiliation: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology , 70376 Stuttgart, Germany.|University of Tübingen , 72074 Tübingen, Germany.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Mürdter
authors.affiliation: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology , 70376 Stuttgart, Germany.|University of Tübingen , 72074 Tübingen, Germany.|Department of Urology, University Hospital Tübingen , 72076 Tübingen, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Rausch
authors.affiliation: Biocrates Life Sciences AG , 6020 Innsbruck, Austria.
authors.forename: Denise
authors.initials: D
authors.lastname: Sonntag
authors.affiliation: Biocrates Life Sciences AG , 6020 Innsbruck, Austria.
authors.forename: Judith
authors.initials: J
authors.lastname: Wahrheit
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital Tübingen , 72076 Tübingen, Germany.
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
authors.affiliation: Department of Urology, University Hospital Tübingen , 72076 Tübingen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Hennenlotter
authors.affiliation: Department of Urology, University Hospital Tübingen , 72076 Tübingen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Bedke
authors.affiliation: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology , 70376 Stuttgart, Germany.|University of Tübingen , 72074 Tübingen, Germany.|Department of Clinical Pharmacology, University Hospital Tübingen , 72076 Tübingen, Germany.|Department of Pharmacy and Biochemistry, University of Tübingen , 72076 Tübingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwab
authors.affiliation: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology , 70376 Stuttgart, Germany.|University of Tübingen , 72074 Tübingen, Germany.
authors.forename: Mathias
authors.identifier: 0000-0001-9017-9021
authors.initials: M
authors.lastname: Haag
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000737:chemistry* / Q000175:diagnosis / Q000473:pathology; D002853:Chromatography, Liquid / Q000379:methods; D006801:Humans; D007668:Kidney / Q000737:chemistry*; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000175:diagnosis / Q000473:pathology; D008055:Lipids / Q000302:isolation & purification*; D055442:Metabolome; D055432:Metabolomics / Q000295:instrumentation / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013552:Swine
chemical_list: D008055:Lipids
keywords: LC−MS; Q-TOF; clear cell renal cell carcinoma (ccRCC); kidney cancer; lipidomics; metabolomics; nontargeted metabolomics; platform comparison; targeted metabolomics; tissue metabolomics