Renal Cancer detection: a translational metabolomics research based on Volatile Organic Compounds fingerprinting
The main goal of this project is to develop a comprehensive bottom-up metabolomics approach focused at identifying suitable urinary biomarkers for early diagnosis of RCC. Few pilot studies have shown the potential of metabolomics for analysis of Volatile Organic Compounds (VOCs) for discrimination of urine of RCC and control patients.
However, urine is a complex biofluid, reflecting a large number of variables causing random statistical noise and hence masking valid information. Hence, we will establish the analytical system and the proof of the concept in model systems (bottom-up approach), before starting tests with human biofluids.
To this purpose, we will evaluate the VOCs profile of RCC in in vitro and ex vivo models with an increasing level of biological complexity: (1) immortalized cell lines of tumor and normal kidney cells; (2) tumoral and adjacent healthy kidney tissues from ccRCC patients who underwent nephrectomy.
This novel approach is expected to establish valid biomarkers, which will be validated in urines from RCC patients. Sophisticated GC-MS methodology will be applied for comprehensive profiling of VOCs. Multivariate statistical analysis will be used for analysis of the data produced by these high-resolution methodologies focused on classifying normal and cancer cells/tissues groups and identification of metabolites that allowed the discrimination of the two groups with high sensitivity and selectivity.
In parallel, a sensor based on the e-nose technology will be applied for fast and effective detection of VOC specific signatures in the in vitro model and urine from patients. The candidate biomarkers will be validated in urine samples of patients from two different populations to prove the translatability of the set of biomarkers. Validated urinary biomarkers will be patented, by the end of the project, for development of a non-invasive diagnostic tool for RCC. For this project, a research group with complementary skills and cooperation experience was organized.
A ICETA/UCIBIO-REQUIMTE Group (proponent institution), with large expertise in the field of GC-MS based metabolomics and in multivariate statistical analysis; a UFP Group, with competence in establishment of immortalized and primary cultures from human kidney tissues; and a IPO Group, that comprises the Service of Urology and the Departments of Genetics and Pathology, that guarantee good access to clinical samples and histological and genetic confirmation of RCC subtype.
This team has outstanding research in the cancer biomarker discovery field strengthening the success of the proposed project, and finally a group of UCIBIO/REQUIMTE from Lisbon to develop a non-invasive diagnostic tool of the CCR to use in the clinic based on a newly developed electronic nose.
- REQUIMTE – Rede de Química e de Tecnologia – Associação
Other institutions related to the project:
- Fundação Ensino e Cultura Fernando Pessoa
- Instituto Português de Oncologia do Porto Francisco Gentil – E.P.E.
- Nova.id.FCT – Associação para a Inovação e Desenvolvimento da FCT
Project supported by:
- Fundação para a Ciência e Tecnologia & Program Portugal 2020
Reference: Project number 30388 – SAICT 2017