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This project aims at uncovering novel cancer biomarkers that can be readily detected by non-invasive methodologies, allowing an early diagnosis of gastric cancer a significant societal problem in Portugal. Together with other patients’ information, the final diagnostic tool tackles the disease in its early development, resulting in enhancing patient’s survival and quality of life (QoL) through less aggressive and invasive therapeutic procedures (see Visual Abstract). Furthermore, it will reduce the health system’s economic burden and potentially the disparities, by empowering citizen, adding information to endoscopy and individualizing management.

This project will be conducted at CINTESIS and UnIC; two well-established research units settled at the Faculdade de Medicina da Universidade do Porto, classified by Fundação para Ciência e Tecnologia (FCT) as Very Good and Excellent, respectively.

Specifically, this will be coordinated by Mário Dinis-Ribeiro, Leader PI of iGO – a research group dedicated to Health Technologies Assessment in Gastrointestinal Oncology and Head of Department of the Gastroenterology Department at Instituto Português de Oncologia do Porto enabling that the proofs-of-concept and technology developments will be available in a specific clinical setting. Moreover, iGO includes health providers working in diverse hospitals and research facilities that may well represent further testing opportunities and dissemination; and there is a physical strategic proximity to other research facilities namely I3S and INESC leveraging the most suitable and innovative clinical approaches sustained by cutting-edge technologies and laboratory research.

One of the main translational questions that our group iGO@CINTESIS has been pursuing over the last decades focuses on the identification of GI cancer-associated biomarkers towards an early screening and tailored surveillance with several works published in this field, that span from assessing the applicability of pepsinogen blood measurement as a minimally invasive gastric cancer screening strategy (Lomba-Viana 2012, Castro 2018) to the identification of susceptibility biomarkers in inflammation-related genes. We recently observed that eight tagSNPS in COX-2-derived PGE2 pathway modulated the susceptibility for gastric cancer development in a Caucasian population from the Northern region of Portugal. We further characterized this pathway and observed an expression dysregulation of PTGS2, HPGD and SLCO2A1 genes in gastric cancer tissues (Lopes 2020). Furthermore, we reported that gastric carcinogenesis progression was associated with an increased TLRs expression, particularly of TRL2 and TLR4, followed by decreased TOLLIP levels (Pimentel-Nunes 2013). We have recently shown that gastric carcinogenesis was associated with a dysbiotic profile, confirming a Helicobacter pylori dominancy in non-atrophic stomachs and progressive dysbiosis throughout gastric carcinogenesis (submitted). Worth highlighting, our team, in a proof-of-concept transcriptomic study and a preliminary analysis, observed the dysregulation of nearly one thousand genes associated with early gastric cancer in Northern Portuguese patients.  Moreover, we also demonstrated the long-term effectiveness of minimal invasive therapy (i.e., endoscopic resection) but still with a significant but incompletely explained rate of metachrous lesions (Pimentel-Nunes 2016).

The project is structured in specific lines:

in RL1, transcriptomic studies will be performed to determine a panel of biomarkers in saliva to non-invasively allow gastric cancer screening and monitoring;

in RL2, the focus is the concept of functional endoscopy, i.e., the purely morphological/imagiological concept of endoscopy will be challenged by adding the information from biomarkers in the gastric mucus (microbiota);

and in RL3, a comprehensive clinical decision rule will be developed by integrating a priori data (clinical, endoscopic and molecular) and with this tailored screening to gastric cancer.

Both for validation of RL1 results and for the assessment of repercussion in gastric dysbiosis in early cancer transcriptome landscape, salivary and gastric mucus’ biomarkers will be correlated; and both will be integrated with clinical and endoscopic data in RL3.

This consortium and unique project will promote further gains in this area of research, contributing to answer to a societal responsibility towards a relevant health problem, especially in the North of Portugal.  We hypothesize that, all together, our findings will clearly improve the knowledge and technologies available for the early diagnosis of gastric cancer and patients surveillance and, due to a clear impact in health-care resources and patients’ burden, will potentially decrease disparities in the access to care by providing the best care to those in need – the final aim for clinical and translational research.

Norte2020 (Portugal 2020)

588,204.54€

588.204,54€

NORTE-01-0145-FEDER-000050

01/04/2021 – 31/03/2023

Mário Dinis Ribeiro (PI), Pedro Filipe Vieira Pimentel Nunes, Joaquim Adelino Correia Ferreira Leite Moreira, Isabel Alexandra Marcos Miranda, André Pedro Leite Martins Lourenço, Diogo Miguel Pereira Libânio Monteiro, Ricardo João Cruz Correia, Pedro Pereira Rodrigues