期刊
CANCER MEDICINE
卷 6, 期 9, 页码 2106-2120出版社
WILEY
DOI: 10.1002/cam4.1109
关键词
Gas chromatography; liquid chromatography; mass spectrometry; metabolic networks and pathways; metabolomics; urinary bladder neoplasms; urothelium
类别
资金
- Case Western Reserve University/Cleveland Clinic CTSA Grant from the National Center for Research Resources (NCRR) [UL1 RR024989]
- KL2 career development award [RR024990]
- Prevent Cancer Foundation Fellowship
Urothelial carcinoma is the most common form of bladder cancer, but pathway changes that occur with stage-wise progression have not been well defined. We used a metabolomics approach to identify potential metabolic pathways uniquely altered in normal urothelium, nonmuscle-invasive bladder cancer (NMIBC), and muscle-invasive bladder cancer (MIBC). We performed global metabolomic profiling using GC-mass spectrometry (MS) and LC-MS platforms to identify metabolite signatures between normal urothelium and high-grade urothelial carcinoma of different stages. Pathways globally dysregulated in cancer relative to normal urothelium included glucose, tricarboxylic acid (TCA) cycle, lipid, amino acid, and nucleotide pathways. Urothelial carcinoma showed elevated glucose utilization for glycolysis and increased sorbitol pathway intermediates, consistent with Warburg effect. Anaplerosis to sustain energy production suggested by increased late TCA cycle intermediates, amino acids, and dipeptides occurs in bladder cancer. Urothelial carcinoma also shows altered membrane lipid membrane metabolism and differential derivation of nucleic acid components pyrimidine and purine. In stage comparison, MIBC appears to preferentially enhance cyclooxygenase (COX) and lipoxygenase (LOX) signaling, increase heme catabolism, and alter nicotinamide adenine dinucleotide (NAD+) synthesis with a possible influence from associated inflammatory cells. We identify numerous metabolomic alterations in NMIBC and MIBC that likely reflect underlying pathway changes. Differential pathway activity may have value in designing stage-specific novel therapeutics in urothelial carcinoma.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据