dc.contributor.author	Fleming, Christina A.
dc.contributor.author	Mohan, Helen M.
dc.contributor.author	O'Leary, Donal P.
dc.contributor.author	Corrigan, M.
dc.contributor.author	Redmond, H. Paul
dc.date.accessioned	2022-03-21T08:33:28Z
dc.date.available	2022-03-21T08:33:28Z
dc.date.issued	2022-03-03
dc.date.updated	2022-03-16T15:53:59Z
dc.description.abstract	Purpose: Metabolomic analysis in colorectal cancer (CRC) is an emerging research area with both prognostic and therapeutic targeting potential. We aimed to identify metabolomic pathway activity prognostic for CRC recurrence and overall survival and cross-reference such metabolomic data with prognostic genomic single-nucleotide polymorphisms (SNPs). Methods: A systematic search of PubMed, Embase and Cochrane Library was performed for studies reporting prognostic metabolomic pathway activity in CRC in keeping with PRISMA guidelines. The QUADOMICS tool was used to assess study quality. MetaboAnalyst software (version4.0) was used to map metabolites that were associated with recurrence and survival in CRC to recognise metabolic pathways and identify genomic SNPs associated with CRC 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. Results: Nine studies met the inclusion criteria, reporting on 1117 patients. 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) was prognostic of CRC recurrence. Increased activity in aspartate metabolism (p < 0.001, FDR = 0.079) and ammonia recycling (p = 0.004, FDR = 0.345) was 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). Conclusions: With a caveat on study heterogeneity, specific metabolites and metabolic pathway activity appear evident in the setting of poor prognostic colorectal cancers and such metabolic signatures are associated with specific genomic SNPs.	en
dc.description.status	Peer reviewed	en
dc.description.version	Accepted Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.citation	Fleming, C. A., Mohan, H. M., O'Leary, D. P., Corrigan, M. and Redmond, H. P. (2022) 'Metabolomic pathway activity with genomic single-nucleotide polymorphisms associated with colorectal cancer recurrence and 5-year overall survival', Journal of Gastrointestinal Cancer. doi: 10.1007/s12029-022-00813-3	en
dc.identifier.doi	10.1007/s12029-022-00813-3	en
dc.identifier.eissn	1941-6636
dc.identifier.issn	1941-6628
dc.identifier.journaltitle	Journal of Gastrointestinal Cancer	en
dc.identifier.uri	https://hdl.handle.net/10468/12941
dc.language.iso	en	en
dc.publisher	Springer Nature Switzerland AG	en
dc.rights	© 2022, the Authors, under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. This is a post-peer-review, pre-copyedit version of an article published in Journal of Gastrointestinal Cancer. The final authenticated version is available online at: https://doi.org/10.1007/s12029-022-00813-3	en
dc.subject	Metabolomics	en
dc.subject	Metabolism	en
dc.subject	Colorectal cancer	en
dc.subject	Genomic SNPs	en
dc.subject	Cancer outcomes	en
dc.title	Metabolomic pathway activity with genomic single-nucleotide polymorphisms associated with colorectal cancer recurrence and 5-year overall survival	en
dc.type	Article (peer-reviewed)	en

Metabolomic pathway activity with genomic single-nucleotide polymorphisms associated with colorectal cancer recurrence and 5-year overall survival

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