Cyclin E1 is a prognostic biomarker and potential therapeutic target in osteosarcoma.

Abstract

While amplified expressed cyclin E1 is a well-known tumorigenic factor and prognostic biomarker in several malignancies, its prognostic predictive potential and function in osteosarcoma is poorly understood. Here we reveal discrete expression pattern, correlation to clinicopathological characteristics and prognosis and overall function of cyclin E1 in osteosarcoma. Sixty-nine osteosarcoma patient tumor specimens were enrolled to construct a tissue microarray to evaluate cyclin E1 expression through immunohistochemical staining. Cyclin E1 expression in osteosarcoma cell lines and fresh tissues was assessed by Western blot. Cyclin E1 gene expression was evaluated using RNA sequencing data acquired from the public database. We correlated staining intensity to clinical characteristics. Cyclin E1 small interfering RNA was used to determine the effect of cyclin E1 silencing on osteosarcoma cell proliferation and chemotherapeutic sensitivity. Sixty-one percent of the osteosarcoma patient specimens in the tissue microarray had high cyclin E1 expression. Cyclin E1 gene was significantly highly expressed in osteosarcoma tissues and cell lines compared to normal tissues. The expression of cyclin E1 positively correlated with disease status, and inversely correlated to prognosis and response to neoadjuvant chemotherapy. The expression of cyclin E1 was an independent prognostic factor for osteosarcoma patients. In addition, silencing cyclin E1 expression in osteosarcoma cells significantly inhibited cell proliferation and increased sensitivity to chemotherapeutics. We conclude that cyclin E1 is overexpressed in osteosarcoma and is a promising biomarker for prognosis and chemotherapeutic response. We confirm aberrant cyclin E1 expression is a potent therapeutic target in osteosarcoma, and its selective inhibition is a rational treatment strategy for osteosarcoma.