NMR-Based Metabolic Profiling:Methods and Application in Cancer Biomarker Discovery.

[摘要] Metabolomics is the study of low molecular weight biochemical compounds that reflect the physiological state of an organism.Metabolic profiling has been increasingly applied in studies of disease due to the altered metabolic profiles in disease states compared with normal states.Thus, the differential metabolites can be used as biomarkers to aid in the diagnosis of specific diseases, alleviating the challenges of the invasive biopsy approach in clinical diagnosis. Metabolic profiling by Nuclear Magnetic Resonance (NMR) spectroscopy was mainly explored here for its high reproducibility and broad coverage of metabolites, including those not amenable to Mass Spectrometry detection.Sample preparation methodologies (solvent extraction approach) were investigated to facilitate the quantification of metabolites in proteinaceous samples such as blood serum as well as improving the ability of NMR resonance assignments of metabolites in complex biological samples such as urine.The sample preparation methods were implemented in the subsequent study of serum metabolite biomarker discovery of prostate cancer.Biopsy positive and biopsy negative sera NMR metabolic profiles were compared and both univariate and multivariate statistical analysis suggest that 2-hydroxyvalerate, glycine, fructose, choline and creatine can be used as potential biomarkers for the diagnosis of prostate cancer.Further analysis to confirm the metabolic pathway of these potential biomarkers that are specific to prostate cancer and validation test utilizing additional cohort of samples, will complement this study and provide therapeutic insights.Urine specimens were also studied for the prostate cancer biomarker discovery in order to establish a non-invasive way of cancer diagnosis.Multiple variable selection approaches were assessed and combined to form the panel of potential urinary biomarkers.At last, we performed NMR-based metabolic profiling of bladder cancer and control urine samples to explore the possibility of using urine samples for the non-invasive detection of bladder cancer.Seven metabolites were statistically significant in differentiating bladder cancer and control samples and further validation of these metabolites is crucial for the establishment of these urinary metabolite biomarkers for clinical diagnosis.

[发布机构] University of Michigan

[效力级别] Metabolic Profiling

[关键词] Cancer Biomarker;Metabolic Profiling;NMR;Chemistry;Science;Chemistry