TY - JOUR
T1 - Metabolic pathway signatures associated with urinary metabolite biomarkers differentiate bladder cancer patients from healthy controls
AU - Kim, Won Tae
AU - Yun, Seok Joong
AU - Yan, Chunri
AU - Jeong, Pildu
AU - Kim, Ye Hwan
AU - Lee, Il Seok
AU - Kang, Ho Won
AU - Park, Sunghyouk
AU - Moon, Sung Kwon
AU - Choi, Yung Hyun
AU - Choi, Young Deuk
AU - Kim, Isaac Yi
AU - Kim, Jayoung
AU - Kim, Wun Jae
N1 - Funding Information:
This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (no. NRF- 2014R1A2A1A09006983 and no. 2014R1A2A2A04007036) (to W.K.), and by NIH grants R01DK100974 (to J.K.).
PY - 2016/7
Y1 - 2016/7
N2 - Purpose: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.
AB - Purpose: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.
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U2 - 10.3349/ymj.2016.57.4.865
DO - 10.3349/ymj.2016.57.4.865
M3 - Article
C2 - 27189278
AN - SCOPUS:84969255734
VL - 57
SP - 865
EP - 871
JO - Yonsei Medical Journal
JF - Yonsei Medical Journal
SN - 0513-5796
IS - 4
ER -