Metabolic Pathway Signatures Associated with Urinary Metabolite Biomarkers Differentiate Bladder Cancer Patients from Healthy Controls

Our previous high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry study identified bladder cancer (BCA)-specific urine metabolites, including carnitine, acylcarnitines, and melatonin.

The objective of the current study was to determine which metabolic pathways are perturbed in BCA, based on our previously identified urinary metabolome.

A total of 135 primary BCA samples and 26 control tissue samples from healthy volunteers were analyzed. The association between specific urinary metabolites and their related encoding genes was analyzed.

Significant alterations in the carnitine-acylcarnitine and tryptophan metabolic pathways were detected in urine specimens from BCA patients compared to those of healthy controls. The expression of eight genes involved in the carnitine-acylcarnitine metabolic pathway (CPT1A, CPT1B, CPT1C, CPT2, SLC25A20, and CRAT) or tryptophan metabolism (TPH1 and IDO1) was assessed by RT-PCR in our BCA cohort (n=135). CPT1B, CPT1C, SLC25A20, CRAT, TPH1, and IOD1 were significantly downregulated in tumor tissues compared to normal bladder tissues (p<0.05 all) of patients with non-muscle invasive BCA, whereas CPT1B, CPT1C, CRAT, and TPH1 were downregulated in those with muscle invasive BCA (p<0.05), with no changes in IDO1 expression.

Alterations in the expression of genes associated with the carnitine-acylcarnitine and tryptophan metabolic pathways, which were the most perturbed pathways in BCA, were determined.

Yonsei medical journal. 2016 Jul [Epub]

Won Tae Kim, Seok Joong Yun, Chunri Yan, Pildu Jeong, Ye Hwan Kim, Il Seok Lee, Ho Won Kang, Sunghyouk Park, Sung Kwon Moon, Yung Hyun Choi, Young Deuk Choi, Isaac Yi Kim, Jayoung Kim, Wun Jae Kim

Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea., Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea., Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea., Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea., Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea., Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea., Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea., College of Pharmacy, Natural Product Research Institute, Seoul National University, Seoul, Korea., School of Food Science and Technology, Chung-Ang University, Anseong, Korea., Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan, Korea., Department of Urology, Graduate School of Medicine, Yonsei University, Seoul, Korea., Section of Urological Oncology, The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA., Department of Surgery, Harvard Medical School, Boston, MA, USA. ., Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea. .

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