Metabolomic Pathway Activity with Genomic Single-Nucleotide Polymorphisms Associated with Colorectal Cancer Recurrence and 5-Year Overall Survival
- Author(s)
- Fleming, CA; Mohan, HM; O'Leary, DP; Corrigan, M; Redmond, HP;
- Details
- Publication Year 2023-03,Volume 54,Issue #1,Page 247-258
- Journal Title
- Journal of Gastrointestinal Cancer
- Publication Type
- Review
- 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.
- Publisher
- Springer Nature
- Keywords
- Humans; Ammonia; *Colorectal Neoplasms/drug therapy; Genomics; Metabolomics/methods; *Polymorphism, Single Nucleotide; Prognosis; Cancer outcomes; Colorectal cancer; Genomic SNPs; Metabolism; Metabolomics
- Department(s)
- Surgical Oncology
- PubMed ID
- 35239102
- Publisher's Version
- https://doi.org/10.1007/s12029-022-00813-3
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-06-28 01:48:28
Last Modified: 2024-07-09 05:25:48