Identification of a potential VOC-biomarker panel in the urine of renal cell carcinoma patients

envie a um amigo share this

Identification of a potential VOC-biomarker panel in the urine of renal cell carcinoma patients

Segunda, 08.05.2017

The analysis of volatile organic compounds (VOCs) in biological samples is one of the most promising approaches in metabolomics in the identification of cancer biomarkers and / or elucidation of pathophysiological pathways. This work, recently published in the Journal of Cellular and Molecular Medicine, aimed to study the volatile metabolomic profile in urine samples from patients with renal cell carcinoma (CCR) and healthy individuals using solid phase microextraction in headspace mode -SPME) followed by gas chromatography coupled to mass spectrometry (GC-MS), with the aim of identifying a potential panel of volatile biomarkers as a non-invasive strategy for the detection of CCR. The results showed the value of urinary volatiles for CCR detection and advanced with the identification of a promising panel of urinary biomarkers for CCR detection.

 

Authors and Affiliations:

Márcia Monteiro - UCIBIO, REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Universidade do Porto, Porto, Portugal.

Nathalie Moreira - REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Universidade do Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal;  CBQF - Centro de Biotecnologia e Química Fina - Laboratório Associado, Faculdade de Biotecnologia, Universidade Católica Portuguesa, Rua Dr. Bernardino de Almeida, 4200-072 Porto, Portugal.

Joana Pinto- UCIBIO, REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Universidade do Porto, Porto, Portugal.

Ana Pires-Luís - Cancer Biology & Epigenetics Group, Centro de Investigação do Instituto Português de Oncologia, Porto, Portugal.

Rui Henrique -  Cancer Biology & Epigenetics Group, Centro de Investigação do Instituto Português de Oncologia, Porto, Portugal; Departamento de Patologia, Instituto Português de Oncologia - Porto, Porto, Portugal; Departamento de Patologia e Imunologia Molecular, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.

Carmen Jerónimo - Cancer Biology & Epigenetics Group, Centro de Investigação do Instituto Português de Oncologia, Porto, Portugal.

Departamento de Patologia e Imunologia Molecular, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.

Maria de Lourdes Bastos - UCIBIO, REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Universidade do Porto, Porto, Portugal.

Ana Gil - CICECO-Instituto de Materiais de Aveiro (CICECO/UA), Departamento de Química, Universidade de Aveiro, Aveiro, Portugal.

Márcia Carvalho - UFP Energy, Environment and Health Research Unit (FP-ENAS), Universidade Fernando Pessoa, Porto, Portugal.

Paula Guedes de Pinho - UCIBIO, REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Universidade do Porto, Porto, Portugal.

 

Abstract:

The analysis of volatile organic compounds (VOCs) emanating from biological samples appears as one of the most promising approaches in metabolomics for the study of diseases, namely cancer. In fact, it offers advantages, such as non-invasiveness and robustness for high throughput applications. The purpose of this work was to study the urinary volatile metabolic profile of patients with renal cell carcinoma (RCC) (n = 30) and controls (n = 37) with the aim of identifying a potential specific urinary volatile pattern as a non-invasive strategy to detect RCC. Moreover, the effect of some confounding factors such as age, gender, smoking habits and body mass index was evaluated as well as the ability of urinary VOCs to discriminate RCC subtypes and stages. A headspace solid-phase microextraction/gas chromatography–mass spectrometry based method was performed, followed by multivariate data analysis. A variable selection method was applied to reduce the impact of potential redundant and noisy chromatographic variables, and all models were validated by Monte Carlo cross-validation and permutation tests. Regarding the effect of RCC on the urine VOCs composition, a panel of 21 descriptive VOCs of RCC was defined, capable of discriminating RCC patients from controls in principal component analysis. Discriminant VOCs were further individually validated in two independent samples sets (nine RCC patients and 12 controls, seven RCC patients with diabetes mellitus type 2) by univariate statistical analysis. Two VOCs were found consistently and significantly altered between RCC and controls (2-oxopropanal and, according to identification using NIST14, 2,5,8-trimethyl-1,2,3,4tetrahydronaphthalene-1-ol), strongly suggesting enhanced potential as RCC biomarkers. Gender, smoking habits and body mass index showed negligible and age-only minimal effects on the urinary VOCs, compared to the deviations resultant from the disease. Moreover, in this cohort, the urinary volatilome did not show ability to discriminate RCC stages and histological subtypes. The results validated the value of urinary volatilome for the detection of RCC and advanced with the identification of potential RCC urinary biomarkers.

 

Journal: Journal of Cellular and Molecular Medicine

 

Link: http://onlinelibrary.wiley.com/doi/10.1111/jcmm.13132/abstract