Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2) is a novel biomarker of myxofibrosarcoma invasion identified by global protein expression profiling

Kazutaka Kikuta, Daisuke Kubota, Akihiko Yoshida, Zhiwei Qiao, Hideo Morioka, Masaya Nakamura, Morio Matsumoto, Hirokazu Chuman, Akira Kawai, Tadashi Kondo

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Myxofibrosarcoma (MFS) is a mesenchymal malignancy characterized by frequent recurrence even after radical wide resection. To optimize therapy for MFS patients, we aimed to identify candidate tissue biomarkers of MFS invasion potential. Invasion characteristics of MFS were evaluated by magnetic resonance imaging and protein expression profiling of primary tumor tissues performed using two-dimensional difference gel electrophoresis (2D-DIGE). Protein expression profiles were compared between invasive and non-invasive tumors surgically resected from 11 patients. Among the 3453 protein spots observed, 59 demonstrated statistically significant difference in intensity (≥ 2-fold) between invasive and non-invasive tumors (p < 0.01 by Wilkoxon test), and were identified by mass spectrometry as 47 individual proteins. Among them, we further focused on discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2), a receptor tyrosine kinase with aberrant expression in malignant tumors. Immunohistochemistry analysis of 21 additional MFS cases revealed that higher DCBLD2 expression was significantly associated with invasive properties of tumor cells. DCBLD2 sensitivity and specificity, and positive and negative predictive values for MFS invasion were 69.2%, 87.5%, 90%, and 63.6%, respectively. The expression level of DCBLD2 was consistent in different portions of tumor tissues. Thus, DCBLD2 expression can be a useful biomarker to evaluate invasive properties of MFS. Further validation studies based on multi-institutional collaboration and comprehensive analysis of DCBLD2 biological functions in MFS are required to confirm its prognostic utility for clinical application.

Original languageEnglish
Pages (from-to)1160-1166
Number of pages7
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1865
Issue number9
DOIs
Publication statusPublished - 2017 Sep 1

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Biomarkers
Tumors
Two-Dimensional Difference Gel Electrophoresis
Neoplasms
Proteins
Tissue
Validation Studies
Receptor Protein-Tyrosine Kinases
Protein Domains
Mass Spectrometry
Immunohistochemistry
Magnetic resonance
Magnetic Resonance Imaging
Electrophoresis
Recurrence
Sensitivity and Specificity
Mass spectrometry
Gels
Cells
Imaging techniques

Keywords

  • Biomarker
  • DCBLD2
  • Invasion
  • Myxofibrosarcoma
  • Two-dimensional difference gel electrophoresis

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2) is a novel biomarker of myxofibrosarcoma invasion identified by global protein expression profiling. / Kikuta, Kazutaka; Kubota, Daisuke; Yoshida, Akihiko; Qiao, Zhiwei; Morioka, Hideo; Nakamura, Masaya; Matsumoto, Morio; Chuman, Hirokazu; Kawai, Akira; Kondo, Tadashi.

In: Biochimica et Biophysica Acta - Proteins and Proteomics, Vol. 1865, No. 9, 01.09.2017, p. 1160-1166.

Research output: Contribution to journalArticle

Kikuta, Kazutaka ; Kubota, Daisuke ; Yoshida, Akihiko ; Qiao, Zhiwei ; Morioka, Hideo ; Nakamura, Masaya ; Matsumoto, Morio ; Chuman, Hirokazu ; Kawai, Akira ; Kondo, Tadashi. / Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2) is a novel biomarker of myxofibrosarcoma invasion identified by global protein expression profiling. In: Biochimica et Biophysica Acta - Proteins and Proteomics. 2017 ; Vol. 1865, No. 9. pp. 1160-1166.
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abstract = "Myxofibrosarcoma (MFS) is a mesenchymal malignancy characterized by frequent recurrence even after radical wide resection. To optimize therapy for MFS patients, we aimed to identify candidate tissue biomarkers of MFS invasion potential. Invasion characteristics of MFS were evaluated by magnetic resonance imaging and protein expression profiling of primary tumor tissues performed using two-dimensional difference gel electrophoresis (2D-DIGE). Protein expression profiles were compared between invasive and non-invasive tumors surgically resected from 11 patients. Among the 3453 protein spots observed, 59 demonstrated statistically significant difference in intensity (≥ 2-fold) between invasive and non-invasive tumors (p < 0.01 by Wilkoxon test), and were identified by mass spectrometry as 47 individual proteins. Among them, we further focused on discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2), a receptor tyrosine kinase with aberrant expression in malignant tumors. Immunohistochemistry analysis of 21 additional MFS cases revealed that higher DCBLD2 expression was significantly associated with invasive properties of tumor cells. DCBLD2 sensitivity and specificity, and positive and negative predictive values for MFS invasion were 69.2{\%}, 87.5{\%}, 90{\%}, and 63.6{\%}, respectively. The expression level of DCBLD2 was consistent in different portions of tumor tissues. Thus, DCBLD2 expression can be a useful biomarker to evaluate invasive properties of MFS. Further validation studies based on multi-institutional collaboration and comprehensive analysis of DCBLD2 biological functions in MFS are required to confirm its prognostic utility for clinical application.",
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AU - Yoshida, Akihiko

AU - Qiao, Zhiwei

AU - Morioka, Hideo

AU - Nakamura, Masaya

AU - Matsumoto, Morio

AU - Chuman, Hirokazu

AU - Kawai, Akira

AU - Kondo, Tadashi

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