TY - JOUR
T1 - Nucleophosmin as a candidate prognostic biomarker of ewing's sarcoma revealed by proteomics
AU - Kikuta, Kazutaka
AU - Tochigi, Naobumi
AU - Shimoda, Tadakazu
AU - Yabe, Hiroki
AU - Morioka, Hideo
AU - Toyama, Yoshiaki
AU - Hosono, Ako
AU - Eppu, Yasuo
AU - Kawai, Akira
AU - Hirohashi, Setsuo
AU - Kondo, Tadashi
N1 - Funding Information:
Discussions with Profs. Tu Guangzhi, Hu Shouxi, Fan Hongrui, Yang Jinghui, and Sun Jinggui greatly improved the quality of a previous version of this paper. Franco Pirajno publishes with the permission of the Director of the Geological Survey of Western Australia. This work was financially supported by the National Natural Science Foundation of China (grant nos. 40425006, 40352003, and 49972035), and the Hundred Young Scientists Program of the Chinese Academy of Sciences.
PY - 2009/4/15
Y1 - 2009/4/15
N2 - Purpose: We aimed to identify novel prognostic biomarkers for Ewing's sarcoma by investigating the global protein expression profile of Ewing's sarcoma patients. Experimental Design: 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.
AB - Purpose: We aimed to identify novel prognostic biomarkers for Ewing's sarcoma by investigating the global protein expression profile of Ewing's sarcoma patients. Experimental Design: 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.
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U2 - 10.1158/1078-0432.CCR-08-1913
DO - 10.1158/1078-0432.CCR-08-1913
M3 - Article
C2 - 19351769
AN - SCOPUS:65349144856
SN - 1078-0432
VL - 15
SP - 2885
EP - 2894
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 8
ER -
