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Erlmeier, F.* ; Sun, N. ; Shen, J. ; Feuchtinger, A. ; Buck, A. ; Prade, V.M. ; Kunzke, T. ; Schraml, P.* ; Moch, H.* ; Autenrieth, M.* ; Weichert, W.* ; Hartmann, A.* ; Walch, A.K.

MALDI mass spectrometry imaging-Diagnostic pathways and metabolites for renal tumor entities.

Oncology 101, 126-133 (2022)
Postprint DOI PMC
Open Access Green
Background: Correct tumor subtyping of primary renal tumors is essential for treatment decision in daily routine. Most of the tumors can be classified based on morphology alone. Nevertheless, some diagnoses are difficult, and further investigations are needed for correct tumor subtyping. Besides histochemical investigations, high-mass-resolution matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can detect new diagnostic biomarkers and hence improve the diagnostic. Patients and Methods: Formalin-fixed paraffin embedded tissue specimens from clear cell renal cell carcinoma (ccRCC, n = 552), papillary renal cell carcinoma (pRCC, n = 122), chromophobe renal cell carcinoma (chRCC, n = 108), and renal oncocytoma (rO, n = 71) were analyzed by high-mass-resolution MALDI fourier-transform ion cyclotron resonance (FT-ICR) MSI. The SPACiAL pipeline was executed for automated co-registration of histological and molecular features. Pathway enrichment and pathway topology analysis were performed to determine significant differences between RCC subtypes. Results: We discriminated the four histological subtypes (ccRCC, pRCC, chRCC, and rO) and established the subtype-specific pathways and metabolic profiles. rO showed an enrichment of pentose phosphate, taurine and hypotaurine, glycerophospholipid, amino sugar and nucleotide sugar, fructose and mannose, glycine, serine, and threonine pathways. ChRCC is defined by enriched pathways including the amino sugar and nucleotide sugar, fructose and mannose, glycerophospholipid, taurine and hypotaurine, glycine, serine, and threonine pathways. Pyrimidine, amino sugar and nucleotide sugar, glycerophospholipids, and glutathione pathways are enriched in ccRCC. Furthermore, we detected enriched phosphatidylinositol and glycerophospholipid pathways in pRCC. Conclusion: In summary, we performed a classification system with a mean accuracy in tumor discrimination of 85.13%. Furthermore, we detected tumor-specific biomarkers for the four most common primary renal tumors by MALDI-MSI. This method is a useful tool in differential diagnosis and biomarker detection.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Chromophobe Renal Cell Carcinoma ; Clear Cell Renal Cell Carcinoma ; Mass Spectrometry Imaging ; Metabolomics ; Papillary Renal Cell Carcinoma ; Renal Oncocytoma
ISSN (print) / ISBN 0030-2414
e-ISSN 1423-0232
Journal Oncology
Quellenangaben Volume: 101, Issue: 2, Pages: 126-133 Article Number: , Supplement: ,
Publisher Karger
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Analytical Pathology (AAP)
Grants Swiss National Science Foundation (SNSF) European Commission
German Research Foundation (DFG)