A powerful machine learning approach to identify interactions of differentially abundant gut microbial subsets in patients with metastatic and non-metastatic pancreatic cancer.

Journal: Gut microbes
PMID:

Abstract

Pancreatic cancer has a dismal prognosis, as it is often diagnosed at stage IV of the disease and is characterized by metastatic spread. Gut microbiota and its metabolites have been suggested to influence the metastatic spread by modulating the host immune system or by promoting angiogenesis. To date, the gut microbial profiles of metastatic and non-metastatic patients need to be explored. Taking advantage of the 16S metagenomic sequencing and the PEnalized LOgistic Regression Analysis (PELORA) we identified clusters of bacteria with differential abundances between metastatic and non-metastatic patients. An overall increase in Gram-negative bacteria in metastatic patients compared to non-metastatic ones was identified using this method. Furthermore, to gain more insight into how gut microbes can predict metastases, a machine learning approach (iterative Random Forest) was performed. Iterative Random Forest analysis revealed which microorganisms were characterized by a different level of relative abundance between metastatic and non-metastatic patients and established a functional relationship between the relative abundance and the probability of having metastases. At the species level, the following bacteria were found to have the highest discriminatory power: , , sp. 619, , and at the genus level, and , and at the family level. Finally, these data were intertwined with those from a metabolomics analysis on fecal samples of patients with or without metastasis to better understand the role of gut microbiota in the metastatic process. Artificial intelligence has been applied in different areas of the medical field. Translating its application in the field of gut microbiota analysis may help fully exploit the potential information contained in such a large amount of data aiming to open up new supportive areas of intervention in the management of cancer.

Authors

  • Annacandida Villani
    Division of Gastroenterology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
  • Andrea Fontana
  • Concetta Panebianco
    Division of Gastroenterology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
  • Carmelapia Ferro
    Division of Gastroenterology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
  • Massimiliano Copetti
  • Radmila Pavlovic
    Proteomics and Metabolomics Facility (ProMeFa), IRCCS San Raffaele Scientific Institute, Milan, Italy.
  • Denise Drago
    Proteomics and Metabolomics Facility (ProMeFa), IRCCS San Raffaele Scientific Institute, Milan, Italy.
  • Carla Fiorentini
    Scientific Direction, Association for Research on Integrative Oncological Therapies (ARTOI), Roma, Italy.
  • Fulvia Terracciano
    Division of Gastroenterology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
  • Francesca Bazzocchi
    Department of General Surgery, Division of General, Gastroenterologic and Minimally Invasive Surgery, GB Morgagni Hospital, Forlì, Italy.
  • Giuseppe Canistro
    Abdominal Surgery Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
  • Federica Pisati
    Histopathology Unit, Cogentech S.C.a.R.L, Milan, Italy.
  • Evaristo Maiello
    Oncology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
  • Tiziana Pia Latiano
    Oncology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
  • Francesco Perri
    Head and Neck Oncology Unit, Istituto Nazionale Tumori IRCCS-Fondazione "G. Pascale", Naples 80131, Italy.
  • Valerio Pazienza
    Division of Gastroenterology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.