title: Interactomic approach for evaluating nucleophosmin-binding proteins as biomarkers for Ewing's sarcoma.
abstract: 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.
authors.affiliation: Division of Pharmaco-proteomics, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Haga
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ogawara
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kubota
authors.forename: Issay
authors.initials: I
authors.lastname: Kitabayashi
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Murakami
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kondo
mesh_terms: D001859:Bone Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D000090243:Nucleophosmin; D011379:Prognosis; D011485:Protein Binding; D060066:Protein Interaction Maps; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012512:Sarcoma, Ewing / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D000090243:Nucleophosmin