Metabolomic Profiling Reveals Potential Markers and Bioprocesses Altered in Bladder Cancer Progression

Nagireddy Putluri, Ali Shojaie, Vihas T. Vasu, Shaiju K. Vareed, Srilatha Nalluri, Vasanta Putluri, Gagan Singh Thangjam, Katrin Panzitt, Christopher T. Tallman, Charles Butler, Theodore R. Sana, Steven M. Fischer, Gabriel Sica, Daniel J. Brat, Huidong Shi, Ganesh S. Palapattu, Yair Lotan, Alon Z. Weizer, Martha K. Terris, Shahrokh F. ShariatGeorge Michailidis, Arun Sreekumar

Research output: Contribution to journalArticle

97 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)7376-7386
Number of pages11
JournalCancer Research
Volume71
Issue number24
DOIs
StatePublished - Dec 15 2011

Fingerprint

Metabolomics
Urinary Bladder Neoplasms
Cytochrome P-450 Enzyme System
Xenobiotics
decitabine
Neoplasms
DNA Methylation
Methylation
Sequence Analysis
Mass Spectrometry
Urinary Bladder
Biomarkers
Urine
Cell Line
Muscles
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Putluri, N., Shojaie, A., Vasu, V. T., Vareed, S. K., Nalluri, S., Putluri, V., ... Sreekumar, A. (2011). Metabolomic Profiling Reveals Potential Markers and Bioprocesses Altered in Bladder Cancer Progression. Cancer Research, 71(24), 7376-7386. https://doi.org/10.1158/0008-5472.CAN-11-1154

Metabolomic Profiling Reveals Potential Markers and Bioprocesses Altered in Bladder Cancer Progression. / Putluri, Nagireddy; Shojaie, Ali; Vasu, Vihas T.; Vareed, Shaiju K.; Nalluri, Srilatha; Putluri, Vasanta; Thangjam, Gagan Singh; Panzitt, Katrin; Tallman, Christopher T.; Butler, Charles; Sana, Theodore R.; Fischer, Steven M.; Sica, Gabriel; Brat, Daniel J.; Shi, Huidong; Palapattu, Ganesh S.; Lotan, Yair; Weizer, Alon Z.; Terris, Martha K.; Shariat, Shahrokh F.; Michailidis, George; Sreekumar, Arun.

In: Cancer Research, Vol. 71, No. 24, 15.12.2011, p. 7376-7386.

Research output: Contribution to journalArticle

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 2011, 'Metabolomic Profiling Reveals Potential Markers and Bioprocesses Altered in Bladder Cancer Progression', Cancer Research, vol. 71, no. 24, pp. 7376-7386. https://doi.org/10.1158/0008-5472.CAN-11-1154
Putluri, Nagireddy ; Shojaie, Ali ; Vasu, Vihas T. ; Vareed, Shaiju K. ; Nalluri, Srilatha ; Putluri, Vasanta ; Thangjam, Gagan Singh ; Panzitt, Katrin ; Tallman, Christopher T. ; Butler, Charles ; Sana, Theodore R. ; Fischer, Steven M. ; Sica, Gabriel ; Brat, Daniel J. ; Shi, Huidong ; Palapattu, Ganesh S. ; Lotan, Yair ; Weizer, Alon Z. ; Terris, Martha K. ; Shariat, Shahrokh F. ; Michailidis, George ; Sreekumar, Arun. / Metabolomic Profiling Reveals Potential Markers and Bioprocesses Altered in Bladder Cancer Progression. In: Cancer Research. 2011 ; Vol. 71, No. 24. pp. 7376-7386.
@article{e7867f87097d4e63aaa007310d6edc55,
title = "Metabolomic Profiling Reveals Potential Markers and Bioprocesses Altered in Bladder Cancer Progression",
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.",
author = "Nagireddy Putluri and Ali Shojaie and Vasu, {Vihas T.} and Vareed, {Shaiju K.} and Srilatha Nalluri and Vasanta Putluri and Thangjam, {Gagan Singh} and Katrin Panzitt and Tallman, {Christopher T.} and Charles Butler and Sana, {Theodore R.} and Fischer, {Steven M.} and Gabriel Sica and Brat, {Daniel J.} and Huidong Shi and Palapattu, {Ganesh S.} and Yair Lotan and Weizer, {Alon Z.} and Terris, {Martha K.} and Shariat, {Shahrokh F.} and George Michailidis and Arun Sreekumar",
year = "2011",
month = "12",
day = "15",
doi = "10.1158/0008-5472.CAN-11-1154",
language = "English (US)",
volume = "71",
pages = "7376--7386",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "24",

}

TY - JOUR

T1 - Metabolomic Profiling Reveals Potential Markers and Bioprocesses Altered in Bladder Cancer Progression

AU - Putluri, Nagireddy

AU - Shojaie, Ali

AU - Vasu, Vihas T.

AU - Vareed, Shaiju K.

AU - Nalluri, Srilatha

AU - Putluri, Vasanta

AU - Thangjam, Gagan Singh

AU - Panzitt, Katrin

AU - Tallman, Christopher T.

AU - Butler, Charles

AU - Sana, Theodore R.

AU - Fischer, Steven M.

AU - Sica, Gabriel

AU - Brat, Daniel J.

AU - Shi, Huidong

AU - Palapattu, Ganesh S.

AU - Lotan, Yair

AU - Weizer, Alon Z.

AU - Terris, Martha K.

AU - Shariat, Shahrokh F.

AU - Michailidis, George

AU - Sreekumar, Arun

PY - 2011/12/15

Y1 - 2011/12/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84255199617&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84255199617&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-11-1154

DO - 10.1158/0008-5472.CAN-11-1154

M3 - Article

C2 - 21990318

AN - SCOPUS:84255199617

VL - 71

SP - 7376

EP - 7386

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 24

ER -