Molecular Characterization of Advanced Colorectal Cancer Using Serum Proteomics and Metabolomics

Abstract Introduction Colorectal cancer (CRC) is a growing public health concern with high mortality rate. However, there are no valid diagnostic biomarkers and few therapeutic strategies available for CRC, especially advanced CRC, since the pathogenic mechanisms remain poorly understood. Objective To comprehensively reveal molecular characterization of advanced CRC, we applied integrated proteomic and metabolomic analyses on serum samples from 20 patients with CRC at stage III or IV. Methods In the present study, we took advantage of nanoscale liquid chromatography and quadrupole time-of-flight tandem mass spectrometry (nanoLC/Q-TOF-MS/MS) and ultraperformance LC/Q-TOF-MS/MS technologies. Results Overall, 551 proteins and 719 metabolites were identified in those serum samples, respectively. Hierarchical clustering analysis indicated much more remarkable diversity in proteomic profiles than metabolomic profiles. Further functional analysis suggested that ten key pathways associated with cancer cell metabolism were dissected including glycolysis/gluconeogenesis, biosynthesis of amino acids, glutathione metabolism, and arachidonic acid metabolism, based on which protein-protein interaction network analysis was thus constructed with 80 proteins and 21 metabolites. Moreover, the regulatory network in advanced CRC was established according to correlation analysis, indicating conserved roles of metabolome and lipids & lipid like molecules in human serum. Nevertheless, three metabolites and two proteins including hydroquinone, leucenol and sphingomyelin were supposed to be potential biomarkers, which were determined to be positively and significantly correlated with CEA and/or CA 19-9.Conclusions Altogether, our work not only extended our understanding on the physiopathology of advanced CRC, but provided potential biomarkers to improve the accuracy of the diagnosis and monitoring of the syndrome.