Fertility preservation in women with ovarian cancer: Finding new pathways: A case-control study

Ali Khodadadian; Yasser Varghaiyan; Emad Babakhanzadeh; Iraj Alipourfard; Saeed Haghi-Daredeh; Amin Ghobadi; Mohsen Hemmati-Dinarvand; Mehrdad Talebi; Nasrin Ghasemi

doi:10.18502/ijrm.v19i2.8474

Fertility preservation in women with ovarian cancer: Finding new pathways: A case-control study

Int J Reprod Biomed. 2021 Feb 21;19(2):157-166. doi: 10.18502/ijrm.v19i2.8474. eCollection 2021 Feb.

Authors

Ali Khodadadian¹, Yasser Varghaiyan², Emad Babakhanzadeh¹, Iraj Alipourfard^{3

4}, Saeed Haghi-Daredeh⁵, Amin Ghobadi⁶, Mohsen Hemmati-Dinarvand⁷, Mehrdad Talebi¹, Nasrin Ghasemi⁸

Affiliations

¹ Department of Medical Genetics, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
² Department of Immunology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
³ Center of Pharmaceutical Sciences, Faculty of Life Sciences, University of Vienna, Vienna, Austria.
⁴ School of Pharmacy, Faculty of Sciences, University of Rome Tor Vergata, Rome, Italy.
⁵ Department of Medical Nanotechnology, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.
⁶ Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
⁷ Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
⁸ Abortion Research Centre, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Abstract

Background: Surgery and chemotherapy are the two most common treatments for cancers, including ovarian cancer. Although most ovarian cancers occur over the age of 45 yr, it may involve younger women and affect their reproductive ability.

Objective: To assess the expression of Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), Forkhead Box O1 (FOXO1), and miR-340 genes in the ovarian cancer tissues as well as ovarian cancer cell lines.

Materials and methods: In this case-control study, 30 ovarian cancer samples (with the average age of 37 $\pm$ 2.5 years) coupled with their non-tumor marginal tissue (as a control) were collected. Proliferated cell lines were treated with several concentrations of cisplatin, and the half maximal inhibitory concentration (IC50) of cisplatin was quantified by MTT-assay. After RNA extraction, cDNA synthesis and qRT-PCR were done. Finally, the results were analyzed.

Results: While the expression levels of miR-340 and FOXO1 genes in tumor samples displayed a significant reduction (p $\leq$ 0.001), the LGR5 gene presented a significant increase in expression (p $\leq$ 0.0001). However, conversely, the expression levels of miR-340 and FOXO1 genes in cisplatin-sensitive cell lines, after 24, 48, and 72 hr of cisplatin treatment, indicated a significant increase (p $\leq$ 0.001) while the expression of LGR5 gene showed a significant decrease in the cisplatin-sensitive cell line (p $<$ 0.05).

Conclusion: The LGR5, FOXO1, and miR-340 genes can be targeted for early diagnosis and more accurate treatment of ovarian cancer and may prevent some of the ovarian cancer complications such as infertility.

Keywords: FOXO1; Female infertility; LGR5; miR-340.; Ovarian cancer.