title: Identification of GRP75 as an independent favorable prognostic marker of neuroblastoma by a proteomics analysis.
abstract: OBJECTIVE
  Neuroblastoma (NB) is a heterogeneous neoplasm. Detailed biological discrimination is critical for the effective treatment of this disease. Because the tumor behavior of NB is closely associated with the histologic state of differentiation, we thus aimed to identify novel differentiation-associated markers of NB with prognostic implication.
  
  
  METHODS
  A human NB cell line SH-SY5Y was used as a model system to explore potential biomarkers for the differentiation of NB by proteomic analyses. Seventy-two NB tumor tissues were subsequently investigated by immunohistochemistry to validate the correlations between the expression of a novel prognostic marker, various clinicopathologic and biological factors, and patient survival.
  
  
  RESULTS
  Using two-dimensional differential gel electrophoresis, we found a total of 24 spots of proteins in SH-SY5Y cells whose expression was enhanced following differentiation. Glucose-regulated protein 75 (GRP75) was unambiguously identified as one of the five proteins that were dramatically up-regulated following differentiation. Immunohistochemical analyses of 72 NB tumor tissues further revealed that positive GRP75 immunostaining is strongly correlated with differentiated histologies (P < 0.001), mass-screened tumors (P = 0.016), and early clinical stages (P < 0.001) but inversely correlated with MYCN amplification (P = 0.010). Univariate and multivariate survival analyses showed that GRP75 expression is an independent favorable prognostic factor.
  
  
  CONCLUSIONS
  The present findings clearly showed that our proteomics-based novel experimental paradigm could be a powerful tool to uncover novel biomarkers associated with the differentiation of NB. Our data also substantiate an essential role of GRP75 in the differentiation of NB.
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, 7 Chung-Shan South Road, Taipei, Taiwan.
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Hsu
authors.forename: Hsinyu
authors.initials: H
authors.lastname: Lee
authors.forename: Hsueh-Fen
authors.initials: HF
authors.lastname: Juan
authors.forename: Yu-Yin
authors.initials: YY
authors.lastname: Shih
authors.forename: Bo-Jeng
authors.initials: BJ
authors.lastname: Wang
authors.forename: Chien-Yuan
authors.initials: CY
authors.lastname: Pan
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
authors.forename: Hsiu-Hao
authors.initials: HH
authors.lastname: Chang
authors.forename: Meng-Yao
authors.initials: MY
authors.lastname: Lu
authors.forename: Kai-Hsin
authors.initials: KH
authors.lastname: Lin
authors.forename: Hong-Shiee
authors.initials: HS
authors.lastname: Lai
authors.forename: Wei-Jao
authors.initials: WJ
authors.lastname: Chen
authors.forename: Yeou-Guang
authors.initials: YG
authors.lastname: Tsay
authors.forename: Yung-Feng
authors.initials: YF
authors.lastname: Liao
authors.forename: Fon-Jou
authors.initials: FJ
authors.lastname: Hsieh
mesh_terms: D014408:Biomarkers, Tumor; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism* / Q000628:therapy; D011379:Prognosis; D020543:Proteome; D040901:Proteomics / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D020543:Proteome; C018551:glucose-regulated proteins