Prognostic significance of metabolomics clusters in extra-pancreatic NETs: Lung NET sub-analysis (A11)

Introduction: Metabolic flexibility is one of the key hallmarks of cancer and metabolites are the final products of this adaptation, reflecting the aberrant changes that support cancer cells proliferation and survival. In a previous metabolomics study carried out by our group, multiplatform untargeted metabolomic profiling (GC-MS, CE-MS and LC-MS) performed on plasma samples from 77 advanced G1-2 extra-pancreatic NET patients demonstrated that these patients have a distinct metabolomic profile, and identified methionine, porphyrin and tryptophan metabolism as the most relevant dysregulated pathways associated with the prognosis of NETs. Furthermore, a 3-metabolite signature was able to stratify patients in 3 distinct prognostic clusters, with cluster 3 associated with the best prognosis.

Aim(s): To evaluate the prognostic significance of this metabolomic signature in the NET lung cohort.

Materials and methods: This sub-analysis included 19 patients with lung NET, 14 patients belonged to cluster 3 and 5 to cluster 1 (no patients belonged to cluster 2 in this cohort).

Results: Cluster 3 was confirmed to be associated with improved prognosis, with 5-year OS rates of 61.9% compared to 40% for cluster 3 vs 1, respectively. Multivariate analysis including age, gender, grade, functionality, time from randomization to study entry and study treatment as covariables confirmed an association of the metabolite clusters with OS (p=0.067).

Conclusion: This study sub-analysis suggests a prognostic value of the metabolomic signature in lung NETs patients, consistent with that observed in the overall study population. These data deserve further evaluation in larger cohorts and may enhance the prognostic stratification of patients for clinical decisions.

Keywords: metabolimics, prognostic biomarker, lung neuroendocrine tumor, metabolomic signature