Urinary metabolomics-based biological model for predicting survival of bladder cancer patients

Among men, bladder cancer (BCA) is the seventh most common cancer worldwide and the fourth most common in developed countries, classifying it as an extremely deleterious disease in need of more research. Although cystoscopy and cytology are the standard diagnostic tools for BCA, the former has low sensitivity for high-grade superficial tumors [i.e., carcinoma in situ] and latter induces poor sensitivity to low-grade tumors.

Therefore, there is a growing interest in the development noninvasive, more accurate, and more efficient methods for the detection of BCA. Recent advances on technological and data analysis have enabled the characterization of metabolites in biofluids, leading to a possible correlation with metabolic dysfunction. Metabolomics has been applied increasingly in the field of toxicology and biomarker research, in particular for cancer diagnosis. Our previous metabolomics study using human urine specimens provided the differentiation model with a 91.3% sensitivity and 92.5% specificity (AUC = 0.937) and suggested that the metabolomic profile correlates with BCA-specific survival time (Oncotarget 2014).

In the present follow up study, we evaluated the relationship between the BCA-associated urinary metabolites and gene expression associated with relevant biological pathways using bladder tissues derived from BCA patients and experimental controls. Alterations gene expressions associated with the carnitine-acylcarnitine and tryptophan metabolic pathways were determined, as these were the most perturbed pathways in BCA. Recent studies reported that metabolites uniquely detected in urine samples from patients with BCA could be a useful biomarker for BCA diagnosis and prognosis. Because the bladder serves as a temporary urine reservoir, analysis of urine metabolites could provide potential candidates of sensitive and specific biomarkers. We hope to continue this research in order to further evaluate a stronger diagnosis and treatment for BCA. These findings were reported in the Yonsei Med J. in 2016 (http://www.ncbi.nlm.nih.gov/pubmed/27189278).

Written By: Jayoung Kim Ph.D.

Biography:
Cedars-Sinai Medical Center (CSMC) is the largest non-profit hospital in the western United States and an academic medical center with a world-renowned faculty and extensive, highly competitive training programs in more than 50 medical specialty and sub-specialty areas. Cedars-Sinai has one of the largest state-of-the-art research facilities of any private hospital in the nation, housed in over 270,000 sq ft of laboratory and laboratory support space. Dr. Jayoung Kim is a translational scientist with extensive experience in benign urinary tract diseases including bladder cancer and interstitial cystitis, with a focus on molecular mechanisms and biomarker discovery. Dr. Kim is a PI of a NIH funded R01 grant (R01DK100974), DoD (Department of Defense, PRMRP), CDC (U01DP006079), U01 grant (U01 DK103260), the Steven Spielberg Discovery Fund in Prostate Cancer Research Career Development Award and U.S.-Egypt Science and Technology Joint Fund Egyptian Science and Technology Development Fund (STDF).

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