Nucleophosmin as a candidate prognostic biomarker of Ewing's sarcoma revealed by proteomics.
OBJECTIVE
We aimed to identify novel prognostic biomarkers for Ewing's sarcoma by investigating the global protein expression profile of Ewing's sarcoma patients.


METHODS
We examined the proteomic profile of eight biopsy samples from Ewing's sarcoma patients using two-dimensional difference gel electrophoresis. Three patients were alive and continuously disease-free over 3 years after the initial diagnosis (good prognosis group) and five had died of the disease within 2 years of the initial diagnosis (poor prognosis group).


RESULTS
The protein expression profiles produced using two-dimensional difference gel electrophoresis consisted of 2,364 protein spots, among which we identified 66 protein spots whose intensity showed >2-fold difference between the two patient groups. Mass spectrometric protein identification showed that the 66 spots corresponded to 53 distinct gene products. Pathway analysis revealed that 31 of 53 proteins, including nucleophosmin, were significantly related to bone tissue neoplasms (P < 0.000001). The prognostic performance of nucleophosmin was evaluated immunohistochemically on an additional 34 Ewing's sarcoma cases. Univariate and multivariate analyses revealed that nucleophosmin expression significantly correlated with overall survival (P < 0.01).


CONCLUSIONS
These results establish nucleophosmin as a candidate of independent prognostic marker for Ewing's sarcoma patients. Measuring nucleophosmin in biopsy samples before treatment may contribute to the effective management of Ewing's sarcoma.
Kikuta
Kazutaka
K
Proteome Bioinformatics Project, National Cancer Center Research Institute, Tokyo, Japan.
Tochigi
Naobumi
N
Shimoda
Tadakazu
T
Yabe
Hiroki
H
Morioka
Hideo
H
Toyama
Yoshiaki
Y
Hosono
Ako
A
Beppu
Yasuo
Y
Kawai
Akira
A
Hirohashi
Setsuo
S
Kondo
Tadashi
T
D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009687:Nuclear Proteins / Q000378:metabolism*; D000090243:Nucleophosmin; D040901:Proteomics; D012512:Sarcoma, Ewing / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult
D014408:Biomarkers, Tumor; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin