Non−Invasive Urinary Metabolomic Study for the Diagnostic Biomarkers
Discovery of Colorectal Cancer (CRC) Using UPLC−MS Technology
Abstract
Background: Colorectal cancer (CRC) ranks as the third most prevalent
malignancy globally, presenting a formidable early diagnostic challenge.
An effective biomarker with high sensitivity and specificity can help
diagnose CRC and improve the chances of successful treatment. Methods:
100 healthy controls and 95 CRC patients( 25 Stage 0/I,30 stage II and
40 stage III based on Clinical stages) were recruited. Subsequently, 195
urine samples were subjected to UPLC-MS analysis. Comparative analysis
was employed to elucidate noteworthy metabolic variances, and pathway
analysis was conducted to unveil perturbed metabolic functions.
Ultimately, metabolic panels for CRC diagnosis were constructed. Result:
A total of 82 metabolites exhibited statistical significance between CRC
patients and healthy controls. Moreover, pathway analysis revealed that
they were associated with Steroid hormone biosynthesis, Nitrogen
metabolism, and D-Glutamine and D-glutamate metabolism. A composite
panel consisting of Retinol, L-β-aspartyl-L-glycine and 21-Deoxycortisol
showed AUCs of 0.933/0.93 in the discovery/validation group. The panel
also showed commendable efficacy in indifferent CRC stages, with an AUC
of 0.918 for stages 0/I, 0.862 for stage II, and 0.845 for stage III.
Conclusions: Urine metabolomecould distinguish CRC from healthy control
and reflect the changes in different stages of CRC. Potential biomarkers
might be developed by targeted metabolomic analysis.