Bladder cancer(BC)is one of the most frequently diagnosed types of urinary cancer.Despite advances in treatment methods,no specific biomarkers are currently in use.Targeted and untargeted profiling of metabolites and ...Bladder cancer(BC)is one of the most frequently diagnosed types of urinary cancer.Despite advances in treatment methods,no specific biomarkers are currently in use.Targeted and untargeted profiling of metabolites and elements of human blood serum from 100 BC patients and the same number of normal controls(NCs),with external validation,was attempted using three analytical methods,i.e.,nuclear magnetic resonance,gold and silver-109 nanoparticle-based laser desorption/ionization mass spectrometry(LDI-MS),and inductively coupled plasma optical emission spectrometry(ICP-OES).All results were subjected to multivariate statistical analysis.Four potential serum biomarkers of BC,namely,isobutyrate,pyroglutamate,choline,and acetate,were quantified with proton nuclear magnetic resonance,which had excellent predictive ability as judged by the area under the curve(AUC)value of 0.999.Two elements,Li and Fe,were also found to distinguish between cancer and control samples,as judged from ICP-OES data and AUC of 0.807(in validation set).Twenty-five putatively identified compounds,mostly related to glycans and lipids,differentiated BC from NCs,as detected using LDI-MS.Five serum metabolites were found to discriminate between tumor grades and nine metabolites between tumor stages.The results from three different analytical platforms demonstrate that the identified distinct serum metabolites and metal elements have potential to be used for noninvasive detection,staging,and grading of BC.展开更多
基金supported mainly by the National Science Center(Poland)(Project SONATA No.:UMO-2018/31/D/ST4/00109)^(1)H NMR spectra were recorded at Montana State University(MSU),Bozeman,USA,on a cryoprobe-equipped 600 MHz(14 T)AVANCE III solution NMR spectrometer housed in MSU's NMR Center.Funding for MSU NMR Center's NMR instruments has been provided in part by the National Institutes of Health Shared Instrumentation Grant program(Grant Nos.:1S10RR13878 and 1S10RR026659)+2 种基金the National Science Foundation(Grant Nos:NSFMRI:DBI-1532078 and NSF-MRI CHE 2018388)the Murdock Charitable Trust Foundation(Grant No.:2015066:MNL)support from the office of the Vice President for Research,Economic Development,and Graduate Education at MSU.
文摘Bladder cancer(BC)is one of the most frequently diagnosed types of urinary cancer.Despite advances in treatment methods,no specific biomarkers are currently in use.Targeted and untargeted profiling of metabolites and elements of human blood serum from 100 BC patients and the same number of normal controls(NCs),with external validation,was attempted using three analytical methods,i.e.,nuclear magnetic resonance,gold and silver-109 nanoparticle-based laser desorption/ionization mass spectrometry(LDI-MS),and inductively coupled plasma optical emission spectrometry(ICP-OES).All results were subjected to multivariate statistical analysis.Four potential serum biomarkers of BC,namely,isobutyrate,pyroglutamate,choline,and acetate,were quantified with proton nuclear magnetic resonance,which had excellent predictive ability as judged by the area under the curve(AUC)value of 0.999.Two elements,Li and Fe,were also found to distinguish between cancer and control samples,as judged from ICP-OES data and AUC of 0.807(in validation set).Twenty-five putatively identified compounds,mostly related to glycans and lipids,differentiated BC from NCs,as detected using LDI-MS.Five serum metabolites were found to discriminate between tumor grades and nine metabolites between tumor stages.The results from three different analytical platforms demonstrate that the identified distinct serum metabolites and metal elements have potential to be used for noninvasive detection,staging,and grading of BC.
