PURPOSE: We aimed to identify novel chemotherapy responsiveness biomarkers for osteosarcoma (OS) by investigating the global protein expression profile of 12 biopsy samples from OS patients. EXPERIMENTAL DESIGN: Six patients were classified as good responders and six as poor responders, according to the Huvos grading system. The protein expression profiles obtained by 2-D DIGE consisted of 2250 protein spots. RESULTS: Among them, we identified 55 protein spots whose intensity was significantly different (Bonferroni adjusted p-value<0.01) between the two patient groups. Mass spectrometric protein identification demonstrated that the 55 spots corresponded to 38 distinct gene products including peroxiredoxin 2 (PRDX 2). Use of a specific antibody against PRDX 2 confirmed the differential expression of PRDX 2 between good and poor responders, while PRDX 2 levels as measured by Western blotting correlated highly with their corresponding 2-D DIGE values. The predictive value of PRDX 2 expression was further confirmed by examining an additional four OS cases using Western blotting. CONCLUSIONS AND CLINICAL RELEVANCE: These results establish PRDX 2 as a candidate for chemotherapy responsiveness marker in OS. Measuring PRDX 2 in biopsy samples before treatment may contribute to more effective management of OS.
PURPOSE: We aimed to identify novel chemotherapy responsiveness biomarkers for osteosarcoma (OS) by investigating the global protein expression profile of 12 biopsy samples from OS patients. EXPERIMENTAL DESIGN: Six patients were classified as good responders and six as poor responders, according to the Huvos grading system. The protein expression profiles obtained by 2-D DIGE consisted of 2250 protein spots. RESULTS: Among them, we identified 55 protein spots whose intensity was significantly different (Bonferroni adjusted p-value<0.01) between the two patient groups. Mass spectrometric protein identification demonstrated that the 55 spots corresponded to 38 distinct gene products including peroxiredoxin 2 (PRDX 2). Use of a specific antibody against PRDX 2 confirmed the differential expression of PRDX 2 between good and poor responders, while PRDX 2 levels as measured by Western blotting correlated highly with their corresponding 2-D DIGE values. The predictive value of PRDX 2 expression was further confirmed by examining an additional four OS cases using Western blotting. CONCLUSIONS AND CLINICAL RELEVANCE: These results establish PRDX 2 as a candidate for chemotherapy responsiveness marker in OS. Measuring PRDX 2 in biopsy samples before treatment may contribute to more effective management of OS.
Authors: H C Whitaker; D Patel; W J Howat; A Y Warren; J D Kay; T Sangan; J C Marioni; J Mitchell; S Aldridge; H J Luxton; C Massie; A G Lynch; D E Neal Journal: Br J Cancer Date: 2013-07-23 Impact factor: 7.640