Nucleophosmin as a Candidate Prognostic Biomarker of Ewing's Sarcoma Revealed by Proteomics

Abstract

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.

Prognostic Role of Nucleophosmin in Colorectal Carcinomas

“…Accordingly, multivariate analysis is not possible. Similar results are also observed in other solid tumors (Tsui et al, 2008;Kikuta et al, 2009;Coutinho-Camillo et al, 2010). Futhermore, in AML mutated NPM also behaves as a favorable prognostic marker for overall survival or disease-free survival (Shahab et al, 2013).…”

“…that the difference of NPM expression was associated with prognosis and also indicated that NPM may be an important prognosis marker in some solid tumors (Tsui et al, 2008;Kikuta et al, 2009;Coutinho-Camillo et al, 2010). A recent study showed NPM overexpression in CRC and the differential expression of NPM1 along the normal colon-adenoma-carcinoma progression (Wong et al, 2013).…”

Identification of proteins differentially expressed in adriamycin-resistant (pumc-91/ADM) and parental (pumc-91) human bladder cancer cell lines by proteome analysis

“…Additionally, NPM1 had been found to be mutated in acute myeloid leukemia (AML; Falini et al 2005;Verhaak et al 2005). Over-expression of NPM1 may be associated with tumor recurrence and progression and indicated a poor prognosis in bladder cancer and Ewing's sarcoma (Tsui et al 2004(Tsui et al , 2008Kikuta et al 2009). There are multiple mechanisms associated with the anti-apoptotic process of NPM1.…”

An Extensive Tumor Array Analysis Supports Tumor Suppressive Role for Nucleophosmin in Breast Cancer

“…29 Here we show that reduced NPM protein expression was associated with poor prognosis and that over-expression of NPM in the MDA-MB-231 breast cancer cells abrogated their growth in soft agar, supporting a tumor suppressive function for NPM in breast cancer. Previously, high NPM expression has been associated with poor prognosis or recurrence in Ewing's sarcoma, 48 hepatocellular carcinoma, 34 bladder cancer, 49 prostate cancer, 28 colon carcinoma, 50 and gastric carcinoma. 51 Intriguingly, where data on NPM expression in the corresponding normal tissue was available in these studies, 28,34,50,51 it was markedly lower than in the cancer tissue (NPM expression in normal tissue was not reported for bladder cancer and Ewing's carcinoma).…”