Identification of ZNF704 as a Novel Oncogene and an Independent Prognostic Marker in Chondrosarcoma.

Abstract

PurposeThe transcription factor zinc finger protein 704 (ZNF704) is implicated in tumorigenesis. However, the underlying role of ZNF704 in the pathogenesis of chondrosarcoma remains not well delineated. This study investigates the expression level, prognostic significance and potential biological function of ZNF704 in human chondrosarcoma.Materials and MethodsThe mRNA and protein levels of ZNF704 in fresh chondrosarcomas and the paired adjacent non-tumor tissues were evaluated using real-time PCR and immunoblotting, respectively. The protein expression of ZNF704 in chondrosarcoma specimens was detected by immunohistochemistry, and the associations among its expression level, clinicopathological characteristics and prognosis were further investigated. Cell viability, colony formation and apoptosis assay were determined in chondrosarcoma cells and a xenograft model with ZNF704 knockdown.ResultsThe expression levels of ZNF704 mRNA and protein in chondrosarcoma tissues were significantly higher than those in the paired adjacent non-tumor tissues and benign cartilage tumors. Clinicopathological analysis revealed that ZNF704 was expressed at higher levels in chondrosarcoma patients with higher histological grade and advanced MSTS stage. We also found that high expression of ZNF704 significantly correlated with a worse overall survival of chondrosarcoma patients. Multivariate Cox regression analysis indicated that ZNF704 was an independent prognostic marker in chondrosarcoma patients. Our in vitro studies demonstrated that knockdown of ZNF704 markedly inhibited chondrosarcoma cell viability, colony formation and induced apoptosis. In a nude mouse xenograft model, ZNF704 knockdown slowed down chondrosarcoma growth by inducing apoptosis in vivo.ConclusionThese findings suggest that ZNF704 may act as a potent oncogene implicated in chondrosarcoma development, and serve as a independent prognostic marker, highlight the potential of ZNF704 as a novel biomarker and therapeutic target for chondrosarcoma.