Plasma exosomal miR-320d, miR-4479, and miR-6763-5p as diagnostic biomarkers in epithelial ovarian cancer

Shiwen Wang; Xingguo Song; Kangyu Wang; Baibing Zheng; Qinghai Lin; Miao Yu; Li Xie; Liang Chen; Xianrang Song

doi:10.3389/fonc.2022.986343

Plasma exosomal miR-320d, miR-4479, and miR-6763-5p as diagnostic biomarkers in epithelial ovarian cancer

Front Oncol. 2022 Dec 14:12:986343. doi: 10.3389/fonc.2022.986343. eCollection 2022.

Authors

Shiwen Wang¹, Xingguo Song¹, Kangyu Wang¹, Baibing Zheng¹, Qinghai Lin¹, Miao Yu², Li Xie¹, Liang Chen³, Xianrang Song^{1

4}

Affiliations

¹ Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
² Department of Clinical Laboratory, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, China.
³ Department of Gynecological Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
⁴ Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.

Abstract

Background: Exosomal miRNA had been proved as the promising biomarkers for multiple cancers including epithelial ovarian cancer (EOC). This study aimed to validate the diagnostic accuracy of exosomal miR-320d, miR-4479, and miR-6763-5p for EOC.

Materials and methods: Exosomes isolated from the plasma by ultracentrifugation were verified using TEM, qNano and western blot. MiRNAs sequencing was used to screen out the differential exosomal miRNAs and miR-320d, miR-4479, and miR-6763-5p were selected as candidates, which were further verified by RT-qPCR in 168 healthy donors and 161 primary EOC patients. Besides, the diagnostic accuracy of these three exosomal miRNAs were evaluated using the receiver operating characteristic curve (ROC).

Results: MiRNAs sequencing revealed 95 differential exosomal miRNAs between EOC patients and healthy donors. Subsequently, exosomal miR-320d, miR-4479, and miR-6763-5p were significantly down regulated in EOC patients compared with healthy controls and benign patients. More importantly, these three miRNAs could serve as circulating diagnostics biomarkers for EOC, possessing areas under the curve (AUC) of 0.6549, 0.7781, and 0.6834, respectively. Moreover, these three exosomal miRNAs levels were closely associated with lymph node metastasis, meanwhile exosomal miR-320d and miR-4479 expression was related to tumor stage.

Conclusion: Exosomal miR-320d, miR-4479, and miR-6763-5p might serve as potential biomarkers for EOC.

Keywords: biomarkers; diagnosis; epithelial ovarian cancer; exosomes; miRNAs.