Interactomic approach for evaluating nucleophosmin-binding proteins as biomarkers for Ewing's sarcoma
Ayako Haga
Division of Pharmaco-proteomics, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan
Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Yamazaki, Noda-shi, Chiba, Japan
Search for more papers by this authorYoko Ogawara
Division of Hematological Malignancy, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorDaisuke Kubota
Division of Pharmaco-proteomics, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorIssay Kitabayashi
Division of Hematological Malignancy, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorYasufumi Murakami
Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Yamazaki, Noda-shi, Chiba, Japan
Search for more papers by this authorCorresponding Author
Tadashi Kondo
Division of Pharmaco-proteomics, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan
Correspondence: Dr. Tadashi Kondo, Division of Pharmacoproteomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
E-mail:[email protected]
Fax: +81-3-3547-5298
Search for more papers by this authorAyako Haga
Division of Pharmaco-proteomics, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan
Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Yamazaki, Noda-shi, Chiba, Japan
Search for more papers by this authorYoko Ogawara
Division of Hematological Malignancy, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorDaisuke Kubota
Division of Pharmaco-proteomics, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorIssay Kitabayashi
Division of Hematological Malignancy, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan
Search for more papers by this authorYasufumi Murakami
Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Yamazaki, Noda-shi, Chiba, Japan
Search for more papers by this authorCorresponding Author
Tadashi Kondo
Division of Pharmaco-proteomics, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan
Correspondence: Dr. Tadashi Kondo, Division of Pharmacoproteomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
E-mail:[email protected]
Fax: +81-3-3547-5298
Search for more papers by this authorAbstract
Nucleophosmin (NPM) is a novel prognostic biomarker for Ewing's sarcoma. To evaluate the prognostic utility of NPM, we conducted an interactomic approach to characterize the NPM protein complex in Ewing's sarcoma cells. A gene suppression assay revealed that NPM promoted cell proliferation and the invasive properties of Ewing's sarcoma cells. FLAG-tag-based affinity purification coupled with liquid chromatography-tandem mass spectrometry identified 106 proteins in the NPM protein complex. The functional classification suggested that the NPM complex participates in critical biological events, including ribosome biogenesis, regulation of transcription and translation, and protein folding, that are mediated by these proteins. In addition to JAK1, a candidate prognostic biomarker for Ewing's sarcoma, the NPM complex, includes 11 proteins known as prognostic biomarkers for other malignancies. Meta-analysis of gene expression profiles of 32 patients with Ewing's sarcoma revealed that 6 of 106 were significantly and independently associated with survival period. These observations suggest a functional role as well as prognostic value of these NPM complex proteins in Ewing's sarcoma. Further, our study suggests the potential applications of interactomics in conjunction with meta-analysis for biomarker discovery.
Supporting Information
As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.
| Filename | Description |
|---|---|
| elps4662-sup-0001-FigureS1.tif218.9 KB | Figure S1 |
| elps4662-sup-0002-FigureS2.tif540.9 KB | Figure S2 |
| elps4662-sup-0003-FigureS3.tif1.5 MB | Figure S3 |
| elps4662-sup-0004-FigureS4.tif573.4 KB | Figure S4 |
| elps4662-sup-0005-TableS1.xlsx14.7 KB | Table S1: List of identified proteins on Venn diagram |
| elps4662-sup-0006-TableS2.xlsx120.2 KB | Table S2: List of NPM binding proteins identified in Ewing's sarcoma cells |
| elps4662-sup-0007-TableS3.xlsx15.3 KB | Table S3: List of NPM binding proteins identified in single Ewing's sarcoma cell line |
| elps4662-sup-0008-TableS4.xlsx13.7 KB | Table S4: List of sources of functional classification for NPM binding proteins |
| elps4662-sup-0009-TableS5.xlsx14.2 KB | Table S5: List of prognostic biomarker candidates in NPM binding proteins |
| elps4662-sup-0010-TableS6.xlsx10.8 KB | Table S6: Clinical data of 32 Ewing's sarcoma patients |
| elps4662-sup-0011-TableS7.xlsx50.6 KB | Table S7: Microarray data of NPM binding proteins in Ewing's sarcoma patients |
| elps4662-sup-0012-TableS8.xlsx15.7 KB | Table S8: Results of multivariate analysis |
| elps4662-sup-0013-TableS9.xlsx9.2 KB | Table S9: References for the proteins in Fig. 4 and Supplementary Fig. 4 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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