Human epididymis protein 4 (HE4) in chemo-response and prognosis of epithelial ovarian cancer

Abstract

Objective: Human epididymis protein 4 (HE4) is a novel biomarker for epithelial ovarian cancer. This study evaluated the role of HE4 in chemo-response and prognosis of epithelial ovarian cancer

Materials and methods: We generated HE4 knockdown cells by transfecting with OVCAR-3, and HE4 overexpressing cells by transfecting with SKOV-3. We assessed the effect of HE4 gene silencing and overexpression on the transformed phenotype by examining cell viability assay after exposure to chemotherapeutic agents, invasion, migration, apoptosis and signaling pathway. We studied the expression of HE4 in ovarian cancer tissue and the prognostic significance of this protein. Cytoplasmic staining was graded for intensity and percentage of positive cells. The grades were multiplied to determine an H-score.

Results: HE4 knockdown cells showed increased sensitivity to paclitaxel and cisplatin. HE4 knockdown inhibited the AKT and Erk pathways. HE4 overexpressing cells showed decreased sensitivity to paclitaxel. HE4 overexpression activated the AKT and Erk pathways. However, neither HE4 knockdown nor overexpression affected invasion, migration and apoptosis. Based on multivariate analysis, the risk of death was significantly higher in patients with an H-score more than 4.

Conclusions: HE4 increases chemoresistance and activates the AKT and Erk pathways. HE4 expression in ovarian cancer tissue is associated with a worse prognosis for epithelial ovarian cancer patients.