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Targeted Quantification of Carbon Metabolites Identifies Metabolic Progression Markers and an Undiagnosed Case of SDH-Deficient Clear Cell Renal Cell Carcinoma in a German Cohort

Authors :
Doreen William
Kati Erdmann
Jonas Ottemöller
Anastasios Mangelis
Catleen Conrad
Mirko Peitzsch
Evelin Schröck
Graeme Eisenhofer
Aristeidis Zacharis
Susanne Füssel
Daniela Aust
Barbara Klink
Susan Richter
Source :
Metabolites, Vol 11, Iss 11, p 764 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

Renal cell carcinoma (RCC) is among the 10 most common cancer entities and can be categorised into distinct subtypes by differential expression of Krebs cycle genes. We investigated the predictive value of several targeted metabolites with regards to tumour stages and patient survival in an unselected cohort of 420 RCCs. Unsupervised hierarchical clustering of metabolite ratios identified two main clusters separated by α-ketoglutarate (α-KG) levels and sub-clusters with differential levels of the oncometabolite 2-hydroxyglutarate (2HG). Sub-clusters characterised by high 2HG were enriched in higher tumour stages, suggesting metabolite profiles might be suitable predictors of tumour stage or survival. Bootstrap forest models based on single metabolite signatures showed that lactate, 2HG, citrate, aspartate, asparagine, and glutamine better predicted the cancer-specific survival (CSS) of clear cell RCC patients, whereas succinate and α-ketoglutarate were better CSS predictors for papillary RCC patients. Additionally, this assay identifies rare cases of tumours with SDHx mutations, which are caused predominantly by germline mutations and which predispose to development of different neoplasms. Hence, analysis of selected metabolites should be further evaluated for potential utility in liquid biopsies, which can be obtained using less invasive methods and potentially facilitate disease monitoring for both patients and caregivers.

Details

Language :
English
ISSN :
22181989
Volume :
11
Issue :
11
Database :
Directory of Open Access Journals
Journal :
Metabolites
Publication Type :
Academic Journal
Accession number :
edsdoj.737c8718eab247f0abc5488e82bb525a
Document Type :
article
Full Text :
https://doi.org/10.3390/metabo11110764