APEX1 Gene Amplification and Its Protein Overexpression in Osteosarcoma: Correlation with Recurrence,Metastasis,and Survival

Abstract

The expression of apurinic/apyrimidinic exonuclease 1 (APEX1) in tumors has been linked with chemoresistance, radioresistance, and shorter patient survival times. We sought to gain insight into the role of APEX1 in human osteosarcoma by evaluation of gene copy number alterations and its protein expression in osteosarcoma patients treated at the Sarcoma Center of Tianjin Cancer Hospital (Tianjin, China). To evaluate the gene copy number alterations of APEX1, we acquired 10 fresh tissue samples from 9 patients and performed whole-genome array-based comparative genomic hybridization (aCGH). We next acquired formalin-fixed and paraffin embedded tissues from 57 well-annotated osteosarcoma cases and performed immunohistochemical analyses for APEX1. APEX1 gene amplification was observed in 50% (5/10) of the osteosarcoma samples. The overexpression of APEX1 protein was detected in 64.9% (37/57) of the osteosarcomas ranging from negative (35.1%, 20/57), weakly positive (35.1%, 20/57), moderate (14%, 8/57) and strongly positive (15.8%, 9/57). The APEX1 expression had significant correlation with osteosarcoma local recurrence and/or metastasis. Moreover, multivariate analysis showed that APEX1 expression was an independent molecular predictor for disease-free survival of patients with osteosarcomas. Our study for the first time showed that APEX1 gene was amplified in osteosarcomas and that APEX1 expression was an independent predictor of the osteosarcoma local recurrence and/or metastasis. Thus, APEX1 may serve as a prognostic marker and potential therapeutic target for osteosarcoma.