RESUMO
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.
Assuntos
Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores/metabolismo , Carcinoma de Células de Transição/genética , Carnitina/análogos & derivados , Estudos de Casos e Controles , Redes e Vias Metabólicas/fisiologia , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias da Bexiga Urinária/genéticaRESUMO
On H1 MRS (magnetic resonance spectroscopy), malignant tumors show higher concentration of metabolite than benign lesions. Lactate double peak was detected in malignant tumor and endometriosis, and more prominent high concentration was demonstrated in endometriosis. Tuboovarian abscesses and salpingitis do not show prominent peak. Dermoid cysts show high levels of lipid peak. Paratubal cyst and follicular cyst can be showed the lipid peak, however, the concentration of lipid is lower than that of dermoid cyst. H1 MRS of ovarian cystic lesions can give valuable information about the presence of metabolites of ovarian cystic lesions.