title: Nuclear Magnetic Resonance metabolomics reveals an excretory metabolic signature of renal cell carcinoma.
abstract: RCC usually develops and progresses asymptomatically and, when detected, it is frequently at advanced stages and metastatic, entailing a dismal prognosis. Therefore, there is an obvious demand for new strategies enabling an earlier diagnosis. The importance of metabolic rearrangements for carcinogenesis unlocked a new approach for cancer research, catalyzing the increased use of metabolomics. The present study aimed the NMR metabolic profiling of RCC in urine samples from a cohort of RCC patients (n = 42) and controls (n = 49). The methodology entailed variable selection of the spectra in tandem with multivariate analysis and validation procedures. The retrieval of a disease signature was preceded by a systematic evaluation of the impacts of subject age, gender, BMI, and smoking habits. The impact of confounders on the urine metabolomics profile of this population is residual compared to that of RCC. A 32-metabolite/resonance signature descriptive of RCC was unveiled, successfully distinguishing RCC patients from controls in principal component analysis. This work demonstrates the value of a systematic metabolomics workflow for the identification of robust urinary metabolic biomarkers of RCC. Future studies should entail the validation of the 32-metabolite/resonance signature found for RCC in independent cohorts, as well as biological validation of the putative hypotheses advanced.
authors.affiliation: UCIBIO@REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Márcia S
authors.initials: MS
authors.lastname: Monteiro
authors.affiliation: CICECO- Instituto de Materiais de Aveiro (CICECO/UA), Departamento de Química, Universidade de Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: António S
authors.initials: AS
authors.lastname: Barros
authors.affiliation: CICECO- Instituto de Materiais de Aveiro (CICECO/UA), Departamento de Química, Universidade de Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Pinto
authors.affiliation: UCIBIO@REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, Porto, Portugal.|FP-ENAS, CEBIMED, Fundação Ensino e Cultura Fernando Pessoa, Porto, Portugal.
authors.forename: Márcia
authors.initials: M
authors.lastname: Carvalho
authors.affiliation: Cancer Biology &Epigenetics Group, Research Center (CI-IPOP) Portuguese Oncology Institute of Porto (IPO of Porto), Porto, Portugal.|Department of Pathology, Portuguese Oncology Institute of Porto (IPO of Porto), Porto, Portugal.
authors.forename: Ana S
authors.initials: AS
authors.lastname: Pires-Luís
authors.affiliation: Cancer Biology &Epigenetics Group, Research Center (CI-IPOP) Portuguese Oncology Institute of Porto (IPO of Porto), Porto, Portugal.|Department of Pathology, Portuguese Oncology Institute of Porto (IPO of Porto), Porto, Portugal.|Department of Pathology and Molecular Immunology-Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Henrique
authors.affiliation: Cancer Biology &Epigenetics Group, Research Center (CI-IPOP) Portuguese Oncology Institute of Porto (IPO of Porto), Porto, Portugal.|Department of Pathology, Portuguese Oncology Institute of Porto (IPO of Porto), Porto, Portugal.
authors.forename: Carmen
authors.initials: C
authors.lastname: Jerónimo
authors.affiliation: UCIBIO@REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Maria de Lourdes
authors.initials: ML
authors.lastname: Bastos
authors.affiliation: CICECO- Instituto de Materiais de Aveiro (CICECO/UA), Departamento de Química, Universidade de Aveiro, 3810-193 Aveiro, Portugal.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gil
authors.affiliation: UCIBIO@REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Guedes de Pinho
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D002292:Carcinoma, Renal Cell / Q000652:urine*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000652:urine*; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: D014408:Biomarkers, Tumor