Proteomic study of malignant pleural mesothelioma by laser microdissection and two-dimensional difference gel electrophoresis identified cathepsin D as a novel candidate for a differential diagnosis biomarker

Mutsumi Hosako, Taika Muto, Yukiko Nakamura, Koji Tsuta, Naobumi Tochigi, Hitoshi Tsuda, Hisao Asamura, Takeshi Tomonaga, Akira Kawai, Tadashi Kondo

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

To investigate the proteomic background of malignancies of the pleura, we examined and compared the proteomic profile of malignant pleural mesothelioma (MPM)(10 cases), lung adenocarcinoma (11 cases), squamous cell carcinoma of the lung (13 cases), pleomorphic carcinoma of the lung (3 cases) and synovial sarcoma (6 cases). Cellular proteins were extracted from specific populations of tumor cells recovered by laser microdissection. The extracted proteins were labeled with CyDye DIGE Fluor saturation dyes and subjected to two-dimensional difference gel electrophoresis (2D-DIGE) using a large format electrophoresis device. Among 3875 protein spots observed, the intensity of 332 was significantly different (Wilcoxon p value less than 0.05) and with more than two-fold inter-sample-group average difference between the different histology groups. Among these 332, 282 were annotated by LC-MS/MS and included known biomarker proteins for MPM, such as calretinin, as well as proteins previously uncharacterized in MPM. Tissue microarray immunohistochemistry revealed that the expression of cathepsin D was lower in MPM than in lung adenocarcinoma (15% vs. 44% of cases respectively in immunohistochemistry). In conclusion, we examined the protein expression profile of MPM and other lung malignancies, and identified cathepsin D to distinguish MPM from most popular lung cancer such as lung adenocarcinoma.

Original languageEnglish
Pages (from-to)833-844
Number of pages12
JournalJournal of Proteomics
Volume75
Issue number3
DOIs
Publication statusPublished - 2012 Jan 4
Externally publishedYes

Keywords

  • Biomarker
  • Laser microdissection
  • Malignant pleural mesothelioma
  • Two-dimensional difference gel electrophoresis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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