Metabolomic NMR fingerprinting to identify and predict survival of patients with metastatic colorectal cancer
Menée sur 153 patients atteints d'un cancer colorectal métastatique et 139 témoins sains, cette étude danoise suggère que l'analyse des métabolites du sérum des patients à l'aide de la technique de résonance magnétique nucléaire du proton pourrait servir de biomarqueur prédictif de la survie
Earlier detection of patients with metastatic colorectal cancer (mCRC) might improve their treatment and survival outcomes. In this study, we used proton nuclear magnetic resonance (1H-NMR) to profile the serum metabolome in mCRC patients and determine whether a disease signature may exist that is strong enough to predict overall survival (OS). In 153 mCRC patients and 139 healthy subjects (HS) from three Danish hospitals, we profiled two independent sets of serum samples in a prospective Phase II study. In the training set, 1H-NMR metabolomic profiling could discriminate mCRC patients from HS with a cross-validated accuracy of 100%. In the validation set, 96.7% of subjects were correctly classified. Patients from the training set with maximally divergent OS were chosen to construct an OS predictor. After validation, patients predicted to have short OS had significantly reduced survival (HR = 3.4; 95% CI, 2.06 to 5.50; P = 1.33 x 10-6). A number of metabolites concurred with the 1H-NMR fingerprint of mCRC, offering insights into mCRC metabolic pathways. Our findings establish that 1H-NMR profiling of patient serum can provide a strong metabolomic signature of mCRC and that analysis of this signature may offer an independent tool to predict overall survival.
Cancer Research , résumé, 2011