Metabolic phenotyping to monitor chronic enteritis canceration.

Abstract

Colorectal cancer (CRC) remains an incurable disease. Previous metabolomic studies show that metabolic signatures in plasma distinguish CRC patients from healthy controls. Chronic enteritis (CE) represents a risk factor for CRC, with a 20 fold greater incidence than in healthy individuals. However, no studies have performed metabolomic profiling to investigate CRC biomarkers in CE. Our aims were to identify metabolomic signatures in CRC and CE and to search for blood-derived metabolite biomarkers distinguishing CRC from CE, especially early-stage biomarkers. In this case-control study, 612 subjects were prospectively recruited between May 2015 and May 2016, and including 539 CRC patients (stage I, 102 cases; stage II, 259 cases; stage III, 178 cases) and 73 CE patients. Untargeted metabolomics was performed to identify CRC-related metabolic signatures in CE. Five pathways were significantly enriched based on 153 differential metabolites between CRC and CE. 16 biomarkers were identified for diagnosis of CRC from CE and for guiding CRC staging. The AUC value for CRC diagnosis in the external validation set was 0.85. Good diagnostic performances were also achieved for early-stage CRC (stage I and stage II), with an AUC value of 0.84. The biomarker panel could also stage CRC patients, with an AUC of 0.72 distinguishing stage I from stage II CRC and AUC of 0.74 distinguishing stage II from stage III CRC. The identified metabolic biomarkers exhibit promising properties for CRC monitoring in CE patients and are superior to commonly used clinical biomarkers (CEA and CA19-9).