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

Research output: Contribution to journalArticle

32 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

Fingerprint

RNA Helicases
Gastrointestinal Stromal Tumors
Biomarkers
Proteomics
Tumors
Adenosine Triphosphate
Neoplasm Metastasis
Surgery
Protein-Tyrosine Kinases
Two-Dimensional Difference Gel Electrophoresis
Gels
Gastrointestinal Tract
Electrophoresis
Neoplasms
Proteins
Genes
Mutation
Tissue
Enzymes
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics

Cite this

Clinical proteomics identified ATP-dependent RNA helicase DDX39 as a novel biomarker to predict poor prognosis of patients with gastrointestinal stromal tumor. / Kikuta, Kazutaka; Kubota, Daisuke; Saito, Tsuyoshi; Orita, Hajime; Yoshida, Akihiko; Tsuda, Hitoshi; Suehara, Yoshiyuki; Katai, Hitoshi; Shimada, Yasuhiro; Toyama, Yoshiaki; Sato, Koichi; Yao, Takashi; Kaneko, Kazuo; Beppu, Yasuo; Murakami, Yasufumi; Kawai, Akira; Kondo, Tadashi.

In: Journal of Proteomics, Vol. 75, No. 4, 02.02.2012, p. 1089-1098.

Research output: Contribution to journalArticle

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, vol. 75, no. 4, pp. 1089-1098. https://doi.org/10.1016/j.jprot.2011.10.005
Kikuta, Kazutaka ; Kubota, Daisuke ; Saito, Tsuyoshi ; Orita, Hajime ; Yoshida, Akihiko ; Tsuda, Hitoshi ; Suehara, Yoshiyuki ; Katai, Hitoshi ; Shimada, Yasuhiro ; Toyama, Yoshiaki ; Sato, Koichi ; Yao, Takashi ; Kaneko, Kazuo ; Beppu, Yasuo ; Murakami, Yasufumi ; Kawai, Akira ; Kondo, Tadashi. / Clinical proteomics identified ATP-dependent RNA helicase DDX39 as a novel biomarker to predict poor prognosis of patients with gastrointestinal stromal tumor. In: Journal of Proteomics. 2012 ; Vol. 75, No. 4. pp. 1089-1098.
@article{85f7c3762a1d49888ecdb514896fbf31,
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.",
keywords = "2D-DIGE, ATP-dependent RNA helicase DDX39, Biomarker, Gastrointestinal stromal tumor, Prognosis",
author = "Kazutaka Kikuta and Daisuke Kubota and Tsuyoshi Saito and Hajime Orita and Akihiko Yoshida and Hitoshi Tsuda and Yoshiyuki Suehara and Hitoshi Katai and Yasuhiro Shimada and Yoshiaki Toyama and Koichi Sato and Takashi Yao and Kazuo Kaneko and Yasuo Beppu and Yasufumi Murakami and Akira Kawai and Tadashi Kondo",
year = "2012",
month = "2",
day = "2",
doi = "10.1016/j.jprot.2011.10.005",
language = "English",
volume = "75",
pages = "1089--1098",
journal = "Journal of Proteomics",
issn = "1874-3919",
publisher = "Elsevier",
number = "4",

}

TY - JOUR

T1 - Clinical proteomics identified ATP-dependent RNA helicase DDX39 as a novel biomarker to predict poor prognosis of patients with gastrointestinal stromal tumor

AU - Kikuta, Kazutaka

AU - Kubota, Daisuke

AU - Saito, Tsuyoshi

AU - Orita, Hajime

AU - Yoshida, Akihiko

AU - Tsuda, Hitoshi

AU - Suehara, Yoshiyuki

AU - Katai, Hitoshi

AU - Shimada, Yasuhiro

AU - Toyama, Yoshiaki

AU - Sato, Koichi

AU - Yao, Takashi

AU - Kaneko, Kazuo

AU - Beppu, Yasuo

AU - Murakami, Yasufumi

AU - Kawai, Akira

AU - Kondo, Tadashi

PY - 2012/2/2

Y1 - 2012/2/2

N2 - 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.

AB - 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.

KW - 2D-DIGE

KW - ATP-dependent RNA helicase DDX39

KW - Biomarker

KW - Gastrointestinal stromal tumor

KW - Prognosis

UR - http://www.scopus.com/inward/record.url?scp=84855886307&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855886307&partnerID=8YFLogxK

U2 - 10.1016/j.jprot.2011.10.005

DO - 10.1016/j.jprot.2011.10.005

M3 - Article

VL - 75

SP - 1089

EP - 1098

JO - Journal of Proteomics

JF - Journal of Proteomics

SN - 1874-3919

IS - 4

ER -