Assinaturas oncomicrobianas para estratificação de doentes com cancro gástrico

Our proposal aims to fill a MAJOR GAP with CLINICAL IMPACT on gastric cancer management by identifying specific biomarkers for improved patient care. Our OBJECTIVE is to establish a novel microbiome-centered stratification strategy tailored for these patients, pursuing the following SPECIFIC AIMS: 1. Identify specific tumor microbiome signatures in gastric cancer. Our research aims to comprehensively understand the microbiome in gastric tumors, including the bacterial and the understudied fungal microbiomes. We will address it with an innovative integration of multiple cutting-edge techniques already established in our Lab [Preliminary data]. In contrast to conventional methods reliant on 16S rRNA sequencing, our research breaks new ground by using RNA analysis to reveal the transcriptionally active microbiome, enhancing resolution to the species level with high-depth metatranscriptomics. The integration of metatranscriptomics with metabolomics and ML algorithms will discern microbiome-specific metabolites, thus advancing our understanding on their functional roles in gastric cancer pathogenesis and increasing the likelihood of finding novel microbial features beyond the limitations of conventional techniques. 2. Establish the influence of the microbiome on the gastric cancer molecular landscape. While previous studies on gastric cancer mainly focused on small patient groups and identified bacteria in the stomach [1], our research aims to go beyond by addressing how both bacterial and fungal communities influence the molecular landscape of gastric tumors. Using advanced genomics and transcriptomics techniques to unveil microbiome and tumor relationships, represents a novel approach, which combined with in-depth protein phenotyping will advance the current state of the art, by revealing the cells and molecular pathways influenced by the tumor-specific microbiome. 3. Determine key tumor microbiome and molecular factors that explain prognosis and response to treatment. Our goal is to address the challenge of understanding prognosis and treatment response in gastric cancer, where current therapies are limited by the absence of reliable biomarkers for patient stratification [PP1;2]. While prior studies mostly focused on tumor molecular aspects [3], our innovative approach goes beyond the current state of the art and integrates multiple tumor data layers with the microbiome. Through multi-omics factor analysis, we aim to uncover hidden relationships across the various omics datasets, shedding light on yet unknown interactions between the gastric cancer microbiome and the tumor. Linking these factors to clinico-pathological patient data to predict disease prognosis and therapeutic outcomes, will provide the means needed to stratify patients more accurately based on their ONCOMICROBIOME biomarkers. 4. Validate the clinical impact of ONCOMICROBIOME biomarkers in independent patient cohorts. In this aim we will validate the most significant oncomicrobiome biomarkers. We will assess biomarker clinical performance in two prospectively recruited gastric cancer patient cohorts from another geographic region, to ensure reliability. Our multidisciplinary team of basic scientists, clinicians, and an oncologist consultant, will confirm biomarker effectiveness in classifying patients and predicting prognosis and treatment response. Ultimately, we expect to contribute to the development of personalized treatment strategies for gastric cancer patients.