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Role of human epididymis protein 4 in chemoresistance and prognosis of epithelial ovarian cancer
Author(s) -
Lee Seungho,
Choi Seowon,
Lee Yookyung,
Chung Donghae,
Hong Suntaek,
Park Nohhyun
Publication year - 2017
Publication title -
journal of obstetrics and gynaecology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 50
eISSN - 1447-0756
pISSN - 1341-8076
DOI - 10.1111/jog.13181
Subject(s) - medicine , paclitaxel , ovarian cancer , cancer research , gene knockdown , protein kinase b , mapk/erk pathway , epididymis , cancer , cell growth , gene silencing , cancer cell , biomarker , cisplatin , oncology , signal transduction , apoptosis , biology , andrology , chemotherapy , microbiology and biotechnology , gene , genetics , sperm , biochemistry
Aim Human epididymis protein 4 (HE4) is a novel biomarker for epithelial ovarian cancer. This study was designed to evaluate the role of HE4 in chemo‐response against anti‐cancer drugs and prognosis of epithelial ovarian cancer. Methods HE4‐depleted cells and HE4‐overexpressing cells were generated. The effect of HE4 gene silencing and overexpression was examined using a cell viability assay after exposure to chemotherapeutic agents and the signaling pathway. We studied the expression of HE4 in ovarian cancer tissue and the prognostic significance. Cytoplasmic staining was graded for intensity and percentage of positive cells. The grades were multiplied to determine an H‐score. Results Knockdown of HE4 in OVCAR‐3 cells resulted in reduction in cell growth and increased sensitivity to paclitaxel and cisplatin compared to control cells. This effect originated from the decreased activation of cell‐growth‐related signaling, such as AKT and Erk mediated by epidermal growth factor (EGF), while overexpression of HE4 resulted in enhanced cell growth and suppressed the anti‐tumorigenic activity of paclitaxel. Activation of AKT and Erk pathways was enhanced in HE4‐overexpressing cells compared to control cells. Based on the results of multivariate analysis, the risk of death was significantly higher in patients with an H‐score > 4. Conclusion HE4 induces chemoresistance against anti‐cancer drugs and activates the AKT and Erk pathways to enhance tumor survival. HE4 expression in ovarian cancer tissue is associated with a worse prognosis for epithelial ovarian cancer patients.