Clinical proteomics identified ATP-dependent RNA helicase DDX39 as a novel biomarker to predict poor prognosis of patients with gastrointestinal stromal tumor

Kazutaka Kikuta, Daisuke Kubota, Tsuyoshi Saito, Hajime Orita, Akihiko Yoshida, Hitoshi Tsuda, Yoshiyuki Suehara, Hitoshi Katai, Yasuhiro Shimada, Yoshiaki Toyama, Koichi Sato, Takashi Yao, Kazuo Kaneko, Yasuo Beppu, Yasufumi Murakami, Akira Kawai, Tadashi Kondo

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37 Citations (Scopus)

Abstract

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal malignancy of the gastrointestinal tract, comprising a wide spectrum from a curable disorder to highly malignant disease. GIST is characterized by tyrosine kinase mutations, and molecular targeting therapies against these abnormal enzymes require prognostic biomarkers. To identify candidate prognostic biomarkers, we examined proteomic features corresponding to metastasis after surgery. Using two-dimensional difference gel electrophoresis with a large format gel, we compared the primary tumor tissues of GIST patients free of metastasis for two years after surgery (eight cases) with those of patients who developed metastasis within one year after surgery (nine cases). We found the intensities of 38 protein spots to differ significantly between the two groups. Mass spectrometric protein identification revealed that these corresponded to 25 unique genes. Immunohistochemical validation demonstrated ATP-dependent RNA helicase DDX39 to be significantly associated with metastasis and poor clinical outcomes in a group of 72 GIST patients. In conclusion, we have established a novel prognostic utility of ATP-dependent RNA helicase DDX39 in GIST. ATP-dependent RNA helicase DDX39, a novel biomarker for GIST likely to be associated with metastatic disease, can identify patients likely to benefit from new therapeutic strategies such as tyrosine kinase inhibitors.

Original languageEnglish
Pages (from-to)1089-1098
Number of pages10
JournalJournal of Proteomics
Volume75
Issue number4
DOIs
Publication statusPublished - 2012 Feb 2

Keywords

  • 2D-DIGE
  • ATP-dependent RNA helicase DDX39
  • Biomarker
  • Gastrointestinal stromal tumor
  • Prognosis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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    Kikuta, K., Kubota, D., Saito, T., Orita, H., Yoshida, A., Tsuda, H., Suehara, Y., Katai, H., Shimada, Y., Toyama, Y., Sato, K., Yao, T., Kaneko, K., Beppu, Y., Murakami, Y., Kawai, A., & Kondo, T. (2012). Clinical proteomics identified ATP-dependent RNA helicase DDX39 as a novel biomarker to predict poor prognosis of patients with gastrointestinal stromal tumor. Journal of Proteomics, 75(4), 1089-1098. https://doi.org/10.1016/j.jprot.2011.10.005