The studies were conducted by Robert Weiss, M.D. of the Cancer Center at the University of California Davis and colleagues at the University’s Departments of Public Health Sciences and Internal Medicine in collaboration with Metabolon scientists.
The first study, “Urine Metabolomic Analysis Identifies Potential Biomarkers and Pathogenic Pathways in Kidney Cancer,” used metabolomics techniques to identify metabolites in the urine of patients with kidney cancer (renal cell carcinoma, RCC) that appear at different levels compared with patients without kidney cancer. The levels of quinolinate, 4-hydroxybenzoate and gentisate, metabolites involved in common biochemical pathways of specific amino acid and energy metabolism, were significantly different in urine from RCC patients. This result is consistent with protein breakdown and utilization as well as the Warburg effect in kidney cancer tumors. Further, the investigators showed that addition of quinolinate, or α-ketoglutarate, which increased significantly in kidney cancer, stimulated growth in RCC cell lines more than addition of gentisate, which decreased.
The article has been published online in OMICS, A Journal of Integrative Biology and may be accessed here
The second study, “Urinary Acyl-carnitines Are Altered in Human Kidney Cancer,” compared urine samples from patients with and without kidney cancer, using metabolomics. This study found increases in urinary acyl-carnitines in patients with kidney cancer, with the highest levels associated with high cancer grades. Analysis of a Caki1 mouse xenograft model of human kidney cancer suggest the acyl-carnitines are from tumor tissue and may reflect alterations in metabolism or in cell component synthesis. Since higher chain length acyl-carnitines have an inhibitory effect on NF-kB activation, these metabolites may also reflect changes in immune surveillance, and may help explain the profound chemotherapy resistance seen with this cancer. This study shows for the first time the value of a novel class of metabolites that may lead to new therapeutic approaches for kidney cancer and may prove useful in future cancer biomarker studies.
The article has been published online in The International Journal of Cancer and may be accessed here
According to Dr. Weiss, “These studies help advance our knowledge of the seventh most common cancer in the Western world, which unfortunately, typically is diagnosed at a late stage when patient survival statistics are grim. Currently there are no useful biofluid markers for this disease, so diagnosis is dependent on imaging techniques that are not generally used for screening. Further evaluation of metabolomics analysis, as well as confirmation of the specific potential biomarkers using a larger cohort will lead to new avenues of kidney cancer diagnosis and therapy.”
“These research findings potentially open a new area of investigation into the metabolic basis of kidney cancer,” said John Ryals, CEO of Metabolon. “We look forward to better understanding tumor metabolism in an effort to provide leading-edge methods to diagnose kidney cancer at an earlier stage, where therapies oftentimes are more effective.”