OncoTargets and Therapy (Sep 2019)
Circulating serum exosomal aHIF is a novel prognostic predictor for epithelial ovarian cancer
Abstract
Xiaoyan Tang,1–3,* Songping Liu,4,* Yinglei Liu,5,* Xiaojing Lin,1–3 Tingting Zheng,1–3 Xin Liu,1–3 Junjun Qiu,1–3 Keqin Hua1–3 1Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, People’s Republic of China; 2Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 3Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, People’s Republic of China; 4Department of Obstetrics and Gynecology, Zhenjiang Maternal and Child Health Hospital, Zhenjiang, Jiangsu 212001, People’s Republic of China; 5Department of Obstetrics and Gynecology, Nantong First People’s Hospital, Nantong, Jiangsu 226001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junjun Qiu; Keqin HuaDepartment of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai 200011, People’s Republic of ChinaTel +86 216 345 5050 ext 8261Fax +86 216 345 5090Email [email protected]; [email protected]: Exosomes are key mediators of cellular communication by transporting molecules, including long noncoding RNAs (lncRNAs), and have been regarded as promising non-invasive biomarkers. This study aimed to evaluate the expression pattern and clinical significance of serum exosomal lncRNA antisense hypoxia inducible factor (aHIF) in epithelial ovarian cancer (EOC).Patients and methods: Sixty-two EOC patients in Obstetrics and Gynecology Hospital of Fudan University were enrolled. The expression levels of aHIF in tissues and serum exosomes were examined by RT-qPCR. The origin of serum exosomal aHIF was explored in vitro and in vivo. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic factors of EOC. A prognostic predictive nomogram was formulated in R software.Results: We isolated exosomes, identified exosomal aHIF in the serum of EOC patients. The expression of serum exosomal aHIF was higher in EOC patients and was correlated with the aHIF level in EOC tissues. In vitro and in vivo, the results indicated that serum exosomal aHIF was derived from tumor cells. Kaplan-Meier survival analysis demonstrated that EOC patients with higher serum exosomal aHIF expression had poorer overall survival. Cox multivariate regression model revealed that FIGO stage, residual tumor size, and serum exosomal aHIF level were independent prognostic factors of EOC. Based on the prognostic value of serum exosomal aHIF, we established a nomogram model that showed a good predictive ability for EOC patients.Conclusion: Serum exosomal aHIF is overexpressed in EOC and can serve as a noninvasive predictive biomarker for unfavorable prognosis.Keywords: epithelial ovarian cancer; EOC, exosome, antisense hypoxia inducible factor, aHIF, nomogram, biomarker
