MCP Danish Cancer Society
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/mcp.M700500-MCP200 on March 13, 2008.
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow All Versions of this Article:
M700500-MCP200v1
7/6/1162    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Glossary
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Google Scholar
Right arrow Articles by Ralhan, R.
Right arrow Articles by Siu, K. W. M.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ralhan, R.
Right arrow Articles by Siu, K. W. M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Molecular & Cellular Proteomics 7:1162-1173, 2008.
© 2008 by The American Society for Biochemistry and Molecular Biology, Inc.

Research

Discovery and Verification of Head-and-neck Cancer Biomarkers by Differential Protein Expression Analysis Using iTRAQ Labeling, Multidimensional Liquid Chromatography, and Tandem Mass Spectrometry*,S

Ranju Ralhan{ddagger},§,¶,||, Leroi V. DeSouza{ddagger},§, Ajay Matta,**, Satyendra Chandra Tripathi, Shaun Ghanny§,{ddagger}{ddagger}, Siddartha Datta Gupta§§, Sudhir Bahadur¶¶ and K. W. Michael Siu{ddagger},§,||||

From the Departments of {ddagger} Chemistry and {ddagger}{ddagger} Mathematics and Statistics and § Centre for Research in Mass Spectrometry, York University, Toronto, Ontario M2J 1P3, Canada and Departments of Biochemistry, §§ Pathology, and ¶¶ Otorhinolaryngology, All India Institute of Medical Sciences, New Delhi 110029, India

Multidimensional LC-MS/MS has been used for the analysis of biological samples labeled with isobaric mass tags for relative and absolute quantitation (iTRAQ) to identify proteins that are differentially expressed in human head-and-neck squamous cell carcinomas (HNSCCs) in relation to non-cancerous head-and-neck tissues (controls) for cancer biomarker discovery. Fifteen individual samples (cancer and non-cancerous tissues) were compared against a pooled non-cancerous control (prepared by pooling equal amounts of proteins from six non-cancerous tissues) in five sets by on-line and off-line separation. We identified 811 non-redundant proteins in HNSCCs, including structural proteins, signaling components, enzymes, receptors, transcription factors, and chaperones. A panel of proteins showing consistent differential expression in HNSCC relative to the non-cancerous controls was discovered. Some of the proteins include stratifin (14-3-3{sigma}); YWHAZ (14-3-3{zeta}); three calcium-binding proteins of the S100 family, S100-A2, S100-A7 (psoriasin), and S100-A11 (calgizarrin); prothymosin {alpha} (PTHA); L-lactate dehydrogenase A chain; glutathione S-transferase Pi; APC-binding protein EB1; and fascin. Peroxiredoxin2, carbonic anhydrase I, flavin reductase, histone H3, and polybromo-1D (BAF180) were underexpressed in HNSCCs. A panel of the three best performing biomarkers, YWHAZ, stratifin, and S100-A7, achieved a sensitivity of 0.92 and a specificity of 0.91 in discriminating cancerous from non-cancerous head-and-neck tissues. Verification of differential expression of YWHAZ, stratifin, and S100-A7 proteins in clinical samples of HNSCCs and paired and non-paired non-cancerous tissues by immunohistochemistry, immunoblotting, and RT-PCR confirmed their overexpression in head-and-neck cancer. Verification of YWHAZ, stratifin, and S100-A7 in an independent set of HNSCCs achieved a sensitivity of 0.92 and a specificity of 0.87 in discriminating cancerous from non-cancerous head-and-neck tissues, thereby confirming their overexpressions and utility as credible cancer biomarkers.

|| Recipient of the NCI, National Institutes of Health-Novartis Translational Cancer Research Fellowship Award of the International Union Against Cancer (UICC) at York University. To whom correspondence may be addressed: Dept. of Chemistry and Centre for Research in Mass Spectrometry, York University, 4700 Keele St., Toronto, Ontario M2J 1P3, Canada. Tel.: 416-650-8021; Fax: 416-736-5936; E-mail: ralhanr{at}yorku.ca

|||| To whom correspondence may be addressed: Dept. of Chemistry and Centre for Research in Mass Spectrometry, York University, 4700 Keele St., Toronto, Ontario M2J 1P3, Canada. Tel.: 416-650-8021; Fax: 416-736-5936; E-mail: kwmsiu{at}yorku.ca


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Mol. Cell. ProteomicsHome page
R. Sirdeshmukh
Proteomics in India: An Overview
Mol. Cell. Proteomics, July 1, 2008; 7(7): 1406 - 1407.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Journal of Biological Chemistry 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2008 by the American Society for Biochemistry and Molecular Biology.