resumo
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.
palavras-chave
TRIMESTER MATERNAL URINE; HUMAN COLORECTAL-CANCER; NMR-BASED METABONOMICS; ATP-CITRATE LYASE; KIDNEY CANCER; MASS-SPECTROMETRY; PROFILING REVEALS; BREAST-CANCER; LUNG-CANCER; HEPATOCELLULAR-CARCINOMA
categoria
Science & Technology - Other Topics
autores
Monteiro, MS; Barros, AS; Pinto, J; Carvalho, M; Pires-Luis, AS; Henrique, R; Jeronimo, C; Bastos, MDL; Gil, AM; de Pinho, PG
nossos autores
Ana Maria Pissarra Coelho Gil
Professor Associado com Agregação
António de Sousa Barros
Bolseiro de pós-Doutoramento
Joana Isabel Monteiro Pinto
Bolseiro de pós-Doutoramentoagradecimentos
This work received financial support from the European Union (FEDER funds POCI/01/0145/FEDER/007728) and National Funds (FCT/MEC, Fundacao para a Ciencia e Tecnologia and Ministerio da Educacao e Ciencia) under the Partnership Agreement PT2020 UID/MULTI/04378/2013. It was also developed within the scope of the project CICECO-Aveiro Institute of Materials, POCI-01-0145-FEDER 007679 (FCT Ref. UID /CTM/50011/2013), financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. The authors acknowledge the Portuguese National NMR Network (RNRMN), supported by Fundacao para a Ciencia e Tecnologia (FCT) and M. Spraul, Bruker BioSpin, Germany, for access to software and spectral databases. M.S.M. and J.P. acknowledge FCT for PhD grants SFRH/BD/80518/2011 and SFRH/BD/73343/2010, respectively.