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

Harsh Pawar, Manoj Kumar Kashyap, Nandini A. Sahasrabuddhe, Santosh Renuse, H. C. Harsha, Praveen Kumar, Jyoti Sharma, Kumaran Kandasamy, Arivusudar Marimuthu, Bipin Nair, Sudha Rajagopalan, Jagadeesha Maharudraiah, Chennagiri Shrinivasamurthy Premalatha, Kariyanakatte Veeraiah Veerendra Kumar, M. Vijayakumar, Raghothama Chaerkady, Thotterthodi Subrahmanya Keshava Prasad, Rekha V. Kumar, Akhilesh Pandey

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

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 performed 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 with 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.

Original languageEnglish (US)
Pages (from-to)510-522
Number of pages13
JournalCancer Biology and Therapy
Volume12
Issue number6
DOIs
StatePublished - Sep 15 2011

Keywords

  • Early detection
  • Esophageal carcinoma
  • Invasion
  • Mass spectrometry
  • Metastasis
  • Progression

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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  • Cite this

    Pawar, H., Kashyap, M. K., Sahasrabuddhe, N. A., Renuse, S., Harsha, H. C., Kumar, P., Sharma, J., Kandasamy, K., Marimuthu, A., Nair, B., Rajagopalan, S., Maharudraiah, J., Premalatha, C. S., Kumar, K. V. V., Vijayakumar, M., Chaerkady, R., Prasad, T. S. K., Kumar, R. V., & Pandey, A. (2011). Quantitative tissue proteomics of esophageal squamous cell carcinoma for novel biomarker discovery. Cancer Biology and Therapy, 12(6), 510-522. https://doi.org/10.4161/cbt.12.6.16833