title: Clinical proteomics identified ATP-dependent RNA helicase DDX39 as a novel biomarker to predict poor prognosis of patients with gastrointestinal stromal tumor.
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.
authors: Division of Pharmacoproteomics, National Cancer Center Research Institute, Japan.
authors: Kazutaka
authors: K
authors: Kikuta
authors: Daisuke
authors: D
authors: Kubota
authors: Tsuyoshi
authors: T
authors: Saito
authors: Hajime
authors: H
authors: Orita
authors: Akihiko
authors: A
authors: Yoshida
authors: Hitoshi
authors: H
authors: Tsuda
authors: Yoshiyuki
authors: Y
authors: Suehara
authors: Hitoshi
authors: H
authors: Katai
authors: Yasuhiro
authors: Y
authors: Shimada
authors: Yoshiaki
authors: Y
authors: Toyama
authors: Koichi
authors: K
authors: Sato
authors: Takashi
authors: T
authors: Yao
authors: Kazuo
authors: K
authors: Kaneko
authors: Yasuo
authors: Y
authors: Beppu
authors: Yasufumi
authors: Y
authors: Murakami
authors: Akira
authors: A
authors: Kawai
authors: Tadashi
authors: T
authors: Kondo
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry*; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D053487:DEAD-box RNA Helicases / Q000096:biosynthesis*; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis / Q000378:metabolism*; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007526:Isoelectric Point; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D000255:Adenosine Triphosphate; C498428:DDX39A protein, human; D053487:DEAD-box RNA Helicases