Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Putluri, N; Shojaie, A; Vasu, VT; Vareed, SK; Nalluri, S; Putluri, V; Thangjam, GS; Panzitt, K; Tallman, CT; Butler, C; Sana, TR; Fischer, SM; Sica, G; Brat, DJ; Shi, H; Palapattu, GS; Lotan, Y; Weizer, AZ; Terris, MK; Shariat, SF; Michailidis, G; Sreekumar, A.
Metabolomic profiling reveals potential markers and bioprocesses altered in bladder cancer progression.
Cancer Res. 2011; 71(24):7376-7386
Doi: 10.1158/0008-5472.CAN-11-1154
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Panzitt Katrin
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Although alterations in xenobiotic metabolism are considered causal in the development of bladder cancer, the precise mechanisms involved are poorly understood. In this study, we used high-throughput mass spectrometry to measure over 2,000 compounds in 58 clinical specimens, identifying 35 metabolites which exhibited significant changes in bladder cancer. This metabolic signature distinguished both normal and benign bladder from bladder cancer. Exploratory analyses of this metabolomic signature in urine showed promise in distinguishing bladder cancer from controls and also nonmuscle from muscle-invasive bladder cancer. Subsequent enrichment-based bioprocess mapping revealed alterations in phase I/II metabolism and suggested a possible role for DNA methylation in perturbing xenobiotic metabolism in bladder cancer. In particular, we validated tumor-associated hypermethylation in the cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) promoters of bladder cancer tissues by bisulfite sequence analysis and methylation-specific PCR and also by in vitro treatment of T-24 bladder cancer cell line with the DNA demethylating agent 5-aza-2'-deoxycytidine. Furthermore, we showed that expression of CYP1A1 and CYP1B1 was reduced significantly in an independent cohort of bladder cancer specimens compared with matched benign adjacent tissues. In summary, our findings identified candidate diagnostic and prognostic markers and highlighted mechanisms associated with the silencing of xenobiotic metabolism. The metabolomic signature we describe offers potential as a urinary biomarker for early detection and staging of bladder cancer, highlighting the utility of evaluating metabolomic profiles of cancer to gain insights into bioprocesses perturbed during tumor development and progression.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Adult -
- Aged -
- Aged, 80 and over -
- Aryl Hydrocarbon Hydroxylases - genetics
- Aryl Hydrocarbon Hydroxylases - metabolism
- Biomarkers, Tumor - urine
- Blotting, Western -
- Cell Line, Tumor -
- Cytochrome P-450 CYP1A1 - genetics
- Cytochrome P-450 CYP1A1 - metabolism
- Cytochrome P-450 CYP1B1 -
- DNA Methylation -
- Disease Progression -
- Female -
- Gene Expression Regulation, Neoplastic -
- Humans -
- Male -
- Mass Spectrometry -
- Metabolomics - methods
- Middle Aged -
- Neoplasm Staging -
- Promoter Regions, Genetic - genetics
- Reverse Transcriptase Polymerase Chain Reaction -
- Urinary Bladder - metabolism
- Urinary Bladder - pathology
- Urinary Bladder Neoplasms - genetics
- Urinary Bladder Neoplasms - metabolism
- Urinary Bladder Neoplasms - urine
- Young Adult -