Analysis of the fecal metagenome in long-term survivors of pancreas cancer
Menée à partir de l'analyse du métagénome d'échantillons fécaux collectés auprès de 16 patients ayant survécu au moins 4 ans après une pancréatectomie et une chimiothérapie pour un cancer du pancréas (délai médian entre pancréatectomie et collecte des échantillons : 6 ans) et auprès de 8 patients supplémentaires (survie médiane sans maladie après traitement : 1,8 ans), cette étude analyse la diversité du microbiome intestinal et identifie ses caractéristiques
Background : The 5-year overall survival of pancreas adenocarcinoma (PCa) remains less than 10%. Clinical and tumor genomic characteristics have not differentiated PCa long-term survivors (LTSs) from unselected patients. Preclinical studies using fecal transplant experiments from LTSs of PCa have revealed delayed tumor growth through unknown mechanisms involving the fecal microbiota. However, features of the fecal microbiome in patients with long-term survival are not well described.
Methods : In this cross-sectional study, comprehensive shotgun metagenomics was performed on stool from PCa patients with long-term survival (n = 16). LTS was defined as > 4 years from pancreatectomy and all therapy without recurrence. LTSs were compared to control patients with PCa who completed pancreatectomy and chemotherapy (n = 8). Stool was sequenced using an Illumina NextSeq500. Statistical analyses were performed in R with MicrobiomeSeq and Phyloseq for comparison of LTSs and controls.
Results : All patients underwent pancreatectomy and chemotherapy before sample donation. The median time from pancreatectomy of 6 years (4–14 years) for LTSs without evidence of disease compared to a median disease-free survival of 1.8 years from pancreatectomy in the control group. No differences were observed in overall microbial diversity for LTSs and controls using Shannon/Simpson indexes. Significant enrichment of species relative abundance was observed in LTSs for the Ruminococacceae family specifically Faecalibacterium prausnitzii species as well as Akkermansia mucinophilia species.
Conclusions : Stool from patients cured from PCa has more relative abundance of Faecalibacterium prausnitzii and Akkermansia mucinophilia. Additional studies are needed to explore potential mechanisms by which the fecal microbiota may influence survival in PCa.
Cancer , résumé, 2023