"Medicina de Precisão & Saúde Digital" Fátima Carneiro i3s/ipatimup & Medical Faculty/ CHS João Porto, Portugal
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1 "Medicina de Precisão & Saúde Digital" Fátima Carneiro i3s/ipatimup & Medical Faculty/ CHS João Porto, Portugal
2 Diabetes & obesity at the crossroads between Oncological and Cardiovascular diseases a system analysis NETwork towards precision medicine Network of emblematic regional research, development & innovation infrastructures, hosted by the FMUP, UnIC, and by CHSJ, ISPUP and IPATIMUP/i3S NORTE FEDER th April 2018
3 Background Cancer and CV disease are the main causes of mortality in Western societies, posing a major threat to healthy aging and an unbearable burden to health care systems Metabolic risk (obesity & diabetes) is highly prevalent and underlies both oncological and CV diseases Phenomapping cardiovascular and oncologic diseases in patients at metabolic risk Pathophysiologic pathway knowledge may reveal novel therapeutic targets
4 Research Lines: Specific Goals: Expand/upgrade biobanks/databases Implement an integrated IT infrastructure Multi-omics and bioinformatics analysis in selected subgroups of patients & population controls Identify causal frameworks with potential intervention/prevention impacts RL1- A multi-omics approach to decipher diabetes-related molecular targets in cancer: a step towards precision medicine (IPATIMUP i3s; PI: Fátima Carneiro) RL2- Cardiovascular phenomapping in the continuum from risk population to end-stage disease (UnIC FMUP; PI: Adelino Leite-Moreira) RL3- Integration of metabolic risk markers into the exposome for prediction and prevention of oncological and CV diseases (ISPUP UP; PI: Henrique Barros)
5 RL2- Cardiovascular phenomapping in the continuum from risk population to end-stage disease (UnIC FMUP; PI: Adelino Leite-Moreira)
6 RL1- A multi-omics approach to decipher diabetes-related molecular targets in cancer: a step towards precision medicine
7 N.-Y. Chia, and P. Tan Ann Oncol 2016;27: Genetic and epigenetic modification of gastric cancer (GC).
8 DIABETES & OBESITY AT THE CROSSROADS BETWEEN ONCOLOGICAL AND CARDIOVASCULAR DISEASES A SYSTEM ANALYSIS NETWORK TOWARDS PRECISION MEDICINE (DOCnet) KLF5/GATA4/GATA6 (Amplifications in 30% of GC patients ) HNF4α (Druggable by the anti-diabetic drug Metformin)
9 IT Platform BigData Ongoing work-rl1
10 IT Platform Big Data Overview Why Big Data? Data Scientists, BI Users, DB Admins Why a new Infrastructure? A growing body of evidence demonstrates that Precision Medicine will need even more data!
11 IT Platform BigData - Ongoing work RL1 Support to Research Line 1 GOALS CHALLENGES CURRENT ACHIEVEMENTS
12 IT Platform BigData - Ongoing work RL1 GOALS Information in "free" text - ex: biomarkers What information do we have available? How can we extract knowledge from it? How can we combine it? Pathological anatomy & Surgery & Drugs & Laboratory analysis &
13 IT Platform BigData - Ongoing work RL1 CHALLENGES Multiple protocols Multiple parameters Protocols that have changed over the years
14 IT Platform BigData - Ongoing work RL1 ACHIEVEMENTS Data Warehouse OLAP Cube Sparse data points Repository of integrated data Online analytical processing,
15 IT Platform BigData - Ongoing work RL1 ACHIEVEMENTS SNOMED DATE TNM BIOMARKERS A N A LY S I S r e c o r d s PATIENT DIAGNOSIS TUMORAL REGRESSION SURGERY
16 The Cancer Genome Atlas (TCGA) project; Nature 2014
17 MSI-high EBV Gene expression of immune response and ECM degradation EBV versus MSI-high (only stat sign results) Immune response ECM degradation 1 7
18 What is new? Gastric Cancer with Lymphoid MSI-H status (16.7%) Better overall survival Immune response Stroma Lesser venous/ lymphatic invasion CD8/CD3R significantly associated with EBV infection EBV infection (66.7%) Younger patients Proximal location /gastric stump Expansive growth Lauren classification: Indeterminate Lower ptnm stage PD-L1/PD-1 immune inhibitory checkpoint PD-L1 expression (33.3%) restricted to EBV+ and MSI-H GCLS Targeted therapies
Molecular Pathology of Gastric Cancer
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