IRISH SOCIETY OF GASTROENTEROLOGY
Poster Winners 2020 - Equal Third Prize
1) Department of Colorectal Surgery, Cork University Hospital, Cork - 2) Department of Academic Surgery, Cork University Hospital, Cork
A systematic review, metabo-meta-analysis and cohort validation of the prognostic value of metabolomics with genomic SNP cross-talk for colorectal cancer recurrence and five year overall survival
Christina A Fleming (1,2) Donal P O'Leary (2,3) Helen Mohan (4) Jennifer Kirwan (5) Henry Paul Redmond (2,6)
1) Department of Colorectal Surgery, Cork University Hospital, Cork 2) Department of Academic Surgery, Cork University Hospital, Cork 3) Bon Secours Hospital, Cork 4) Department of Colorectal Surgery, St. Vincent's University Hospital, Dublin 5) Metabolomics Centre, Berlin Institute of Health, Max Delbruch Centre for Molecular Medicine, Berlin 6) Surguvant Research Centre, Cork University Hospital, Cork
Metabolomic analysis in colorectal cancer(CRC)is an emerging research area.
To identify prognostic metabolomic signatures for CRC recurrence and overall survival and cross-reference this data with prognostic genomic single nucleotide polymorphisms(SNPs).
A systematic review of studies utilising metabolomics to identify patients at risk of cancer recurrence and poor survival outcomes in CRC was performed in keeping with PRISMA guidelines. The QUADOMICS tool was used to assess study quality. MetaboAnalyst software, version 4.0 was used to perform metabolic pathway enrichment and identify genomic SNPs associated with colorectal cancer prognosis, referencing the following databases: Human Metabolome Database(HMDB), the Small Molecule Pathway Database(SMPDB), PubChem and Kyoto Encyclopaedia of Genes and Genomes(KEGG)Pathway Database. Metabolomic findings were validated in a population of Irish colon cancer patients.
Nine studies met the inclusion criteria, reporting on 1117 patients and validation performed in 24 colon cancer patients with five-year follow-up. Increased metabolic activity in the urea cycle(p=0.002,FDR-0.198) ammonia recycling(p=0.004,FDR=0.359)and glycine and serine metabolism(p=0.004,FDR=0.374)were prognostic of CRC recurrence. Increased activity in aspartate metabolism(p=8.13E-04,FDR=0.079)and ammonia recycling(p=0.004,FDR=0.345)were prognostic of survival. Eight resulting SNPs were prognostic for CRC recurrence(Rs2194980, Rs1392880, Rs2567397, Rs715, Rs169712, Rs2300701, Rs313408, Rs7018169) and three for survival(Rs2194980, Rs169712, RS12106698) of which two overlapped with recurrence(Rs2194980, Rs169712).
Specific metabolites and metabolic pathways are dysregulated in the setting of poor prognostic colorectal cancers and such metabolic signatures are associated with specific genomic SNPs. These findings provide a platform for prognostic biomarker discovery and development in colorectal cancer as well as identify potential for therapeutic targeting.