Quantitative tissue proteomics of esophageal squamous cell carcinoma for novel biomarker discovery

Esophageal squamous cell carcinoma (ESCC) is among the top ten most frequent malignancies worldwide. In this study, our objective was to identify potential biomarkers for ESCC through a quantitative proteomic approach using the isobaric tags for relative and absolute quantitation (iTRAQ) approach. W...

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Published in:	Cancer biology & therapy Vol. 12; no. 6; pp. 510 - 522
Main Authors:	Pawar, Harsh, Kashyap, Manoj Kumar, Sahasrabuddhe, Nandini A., Renuse, Santosh, Harsha, H. C., Kumar, Praveen, Sharma, Jyoti, Kandasamy, Kumaran, Marimuthu, Arivusudar, Nair, Bipin, Rajagopalan, Sudha, Maharudraiah, Jagadeesha, Premalatha, Chennagiri Shrinivasamurthy, Kumar, Kariyanakatte Veeraiah Veerendra, Vijayakumar, M., Chaerkady, Raghothama, Prasad, Thotterthodi Subrahmanya Keshava, Kumar, Rekha V., Pandey, Akhilesh
Format:	Journal Article
Language:	English
Published:	United States Taylor & Francis 15-09-2011 Landes Bioscience
Subjects:	Binding Biology Biomarkers, Tumor - metabolism Bioscience Calcium Cancer Carcinoma, Squamous Cell - diagnosis Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Cell Cycle early detection Early Detection of Cancer esophageal carcinoma Esophageal Neoplasms - diagnosis Esophageal Neoplasms - metabolism Esophageal Neoplasms - pathology Humans invasion Landes mass spectrometry metastasis Organogenesis Plectin - metabolism progression Protein Disulfide-Isomerases - metabolism Proteins Proteome - metabolism Research Paper Saposins - metabolism Tandem Mass Spectrometry
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Summary:	Esophageal squamous cell carcinoma (ESCC) is among the top ten most frequent malignancies worldwide. In this study, our objective was to identify potential biomarkers for ESCC through a quantitative proteomic approach using the isobaric tags for relative and absolute quantitation (iTRAQ) approach. We compared the protein expression profiles of ESCC tumor tissues with the corresponding adjacent normal tissue from ten patients. LC-MS/MS analysis of strong cation exchange chromatography fractions was carried out on an Accurate Mass QTOF mass spectrometer, which led to the identification of 687 proteins. In all, 257 proteins were identified as differentially expressed in ESCC as compared to normal. We found several previously known protein biomarkers to be upregulated in ESCC including thrombospondin 1 (THBS1), periostin 1 (POSTN) and heat shock 70 kDa protein 9 (HSPA9) confirming the validity of our approach. In addition, several novel proteins that had not been reported previously were identified in our screen. These novel biomarker candidates included prosaposin (PSAP), plectin 1 (PLEC1) and protein disulfide isomerase A 4 (PDIA4) that were further validated to be overexpressed by immunohistochemical labeling using tissue microarrays. The success of our study shows that this mass spectrometric strategy can be applied to cancers in general to develop a panel of candidate biomarkers, which can then be validated by other techniques.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Current address: CeMM Research Center for Molecular Medicine; Vienna, Austria
ISSN:	1538-4047 1555-8576
DOI:	10.4161/cbt.12.6.16833