MAPI-INT “Ricerca di marcatori precoci di ischemia intestinale. Studio prospettico osservazionale”

Report Summary

POR CREO FESR 2007-2013 – LINEA DI INTERVENTO 1.1C

Final Result

In emergency rooms, especially in the case of acute symptoms, the central dogma of patients’ treatment effectiveness consists of rapid disease diagnosis and subsequent targeted cure. Personalized medicine is progressively acquiring importance for both of these purposes and for drug development. In turn, a deeper knowledge of each individual’s metabolome is becoming important for defining individual phenotypes. In recent years, analysis of the human metabolome through the systematic study of bio-specimens (biofluids, tissues, etc.) has strongly developed.

Precision medicine may significantly contribute to rapid disease diagnosis and targeted therapy, but relies on the availability of detailed, subject specific, clinical information. Proton nuclear magnetic resonance (1H–NMR) spectroscopy of body fluids can extract individual metabolic fingerprints.

In this project, we studied 64 patients admitted to the Florence main hospital emergency room with severe abdominal pain. A blood sample was drawn from each patient at admission, and the corresponding sera underwent 1H–NMR metabolomics fingerprinting. Unsupervised Principal Component Analysis (PCA) analysis showed a significant discrimination between a group of patients with symptoms of upper abdominal pain and a second group consisting of patients with diffuse abdominal/intestinal pain. Prompted by this observation, supervised statistical analysis (Orthogonal Partial Least Squares–Discriminant Analysis (OPLS-DA)) showed a very good discrimination (>90%) between the two groups of symptoms. This is a surprising finding, given that neither of the two symptoms points directly to a specific disease among those studied here. Actually herein, upper abdominal pain may result from either symptomatic gallstones, cholecystitis, or pancreatitis, while diffuse abdominal/intestinal pain may result from either intestinal ischemia, strangulated obstruction, or mechanical obstruction. Although limited by the small number of samples from each of these six conditions, discrimination of these diseases was attempted. In the first symptom group, >70% discrimination accuracy was obtained among symptomatic gallstones, pancreatitis, and cholecystitis, while for the second symptom group >85% classification accuracy was obtained for intestinal ischemia, strangulated obstruction, and mechanical obstruction. No single metabolite stands up as a possible biomarker for any of these diseases, while the contribution of the whole 1H–NMR serum fingerprint seems to be a promising candidate, to be confirmed on larger cohorts, as a first-line discriminator for these diseases.

Publications

Fingerprinting Acute Digestive Diseases by Untargeted NMR Based Metabolomics, Panteleimon G. Takis, Antonio Taddei, Riccardo Pini, Stefano Grifoni, Francesca Tarantini, Paolo Bechi and Claudio Luchinat. Int. J. Mol. Sci. 2018, 19(11), 3288; doi: 10.3390/ijms19113288

 

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