AUA 2018: Use of Urinary Metabolomics to Identify High-Risk Clear Cell Renal Cell Carcinoma

San Francisco, CA USA ( Mohit Gupta, MD, a urologic oncologist at John Hopkins University of Medicine, presented a study regarding metabolomic markers that may identify and differentiate high-risk clear cell RCC from benign tumors. Dr. Gupta began the presentation by introducing the importance of metabolomics to identify discrepancies within current pathways known to urologic oncology. Although these pathways have been studied and used for different types of cancers, specific markers within urine of patients with ccRCC have not been clearly identified. Dr. Gupta and his research team have been able to successfully differentiate specific signatures between urine samples from patients with ccRCC and benign tumors.

This IRB-approved study consisted of a cohort of 66 urine samples of patients with ccRCC, where the urine was collected prior to their surgery. All patients underwent a partial or radical nephrectomy. The research team identified the high-risk ccRCC as grade III-IV, while and indolent tumors were classified as grade I-II. Benign tumors were also evaluated in this cohort. Specific particulates and markers within the urine samples were analyzed using capillary electrophoresis mass spectrometry in pathology and 69 metabolites were identified and measured. Significant identifications were plotted and evaluated using Welch & primes t-test for each of the three index pathology groups.

Of the 66 urine samples analyzed in the study, 30 patients were identified as high-risk RCC patients, 19 patients were identified as those with indolent lesions, and 17 were identified as patients with benign tumors. One of the most significant markers Dr. Gupta’s team profiled between these three groups was the higher concentrations of specific amino acids in indolent tumors when compared to benign tumors (p<0.01). In indolent lesions, there was an increase in phenylalanine (+ 42.2%), tyrosine (+ 52.5%), tryptophan (+ 42.7%), and lysine (+ 66%). Another significant difference was found between high-risk RCCs and benign tumors (p<0.01). The following differences were found between benign and high-risk lesions: hypoxanthine (- 42%), threnodic acid (+ 26%) EAP (+ 133%) and glycerol-3-phosphate (+ 110%). The final significant difference was found between high-risk RCCs and indolent lesion (p<0.01). The following differences were identified: betaine (- 63%), hydrouracil (- 36%), N-Ac Gln (- 56%), histidine (- 42%), and 2-aminoisobutyrate (- 47%).

To conclude, Dr. Gupta further discussed the importance of specific metabolomic profiles that may help identify the differences between high-risk RCC, benign, and indolent lesions. Not only can these markers distinguish within a specific type of tumor, but this method could also evaluate the difference between high-risk cancers with benign cancers. It is important to bring up the promising use of this method within clinical settings. However, further research must be carried out before it become available for hospital use

Presented by: Mohit Gupta, MD

Written by: Sherry Lu, Department of Urology, University of California-Irvine at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA