Metabolomic profile of neuroendocrine tumors identifies methionine, porphyrin, and tryptophan metabolisms as key dysregulated pathways associated with patient survival
Authors' conclusion
We identified a metabolomic signature that improves prognostic stratification of NET patients beyond classical prognostic factors for clinical decisions. The enriched metabolic pathways identified reveal novel tumor vulnerabilities that may foster the development of new therapeutic strategies for these patients.
Study context
- Population
- Patients with G1–2 extra-pancreatic neuroendocrine tumors (NETs) enrolled in the AXINET trial; plasma samples
- Participants
- 77 vs 68
- Comparison
- NET patients vs non-cancer controls; prognostic value of metabolites
- Studyn = 77
- Controln = 68reference
- Primary endpoint
- Prognostic value of differential metabolites for PFS and OS
Methodological detailssecondary analysis of the AXINET trial cohort, multiplatform untargeted metabolomics (GC-MS, CE-MS, LC-MS), univariate and multivariate analyses adjusted for multiple testing and confounders
- Secondary analysis of the AXINET trial cohort
- Multiplatform untargeted metabolomics (GC-MS, CE-MS, LC-MS)
- Univariate and multivariate analyses adjusted for multiple testing and confounders
Primary result
As reported in the abstract
Metabolites associated with PFS and/or OS
- Differential metabolites in NET patients
- 155
- Metabolites significantly associated with progression-free survival (PFS) and/or overall survival (OS)
- 34
- Associated with PFS
- 16
- Associated with OS
- 27
- Independent prognostic factors in multivariate analysis
- 13
- Significant impact on both PFS and OS
- 3
Further findings
Prognostic groups by unsupervised clustering of 3 metabolites: 1-year PFS
- 1-year PFS across 3 prognostic groups
- 71.1%, 47.7%, and 15.4% (P = .012)
Prognostic groups by unsupervised clustering of 3 metabolites: 5-year OS
- 5-year OS across 3 prognostic groups
- 69.7%, 32.5%, and 27.7% (P = .003)
Pathway analysis (Metabolite Set Enrichment Analysis (MSEA) and Metabolite Pathway Analysis (MPA)) of 13-metabolite signature
- Methionine, porphyrin and tryptophan metabolisms were the 3 most relevant dysregulated pathways associated with NET prognosis
Original publication
Metabolomic profile of neuroendocrine tumors identifies methionine, porphyrin, and tryptophan metabolisms as key dysregulated pathways associated with patient survival. Eur J Endocrinol. Published 30 November 2023. doi:10.
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