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

Khodadadian A, Ali Khodadadian, Yasser Varghaiyan, Varghaiyan Y, Emad Babakhanzadeh, Babakhanzadeh E, Alipourfard I, Iraj Alipourfard, Saeed Haghi-Daredeh, Haghi-Daredeh S, Ghobadi A, Amin Ghobadi, Mohsen Hemmati-Dinarvand, Hemmati-Dinarvand M, Talebi M, Mehrdad Talebi, Nasrin Ghasemi
International journal of reproductive biomedicine · 2021 · vol. 19(2) , pp. 157–166 · doi:10.18502/ijrm.v19i2.8474 · PMID:33718760 · PMC7922293
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This case-control study found that LGR5 is upregulated while FOXO1 and miR-340 are downregulated in ovarian cancer tissues, with cisplatin treatment reversing these expression patterns to potentially mitigate infertility complications.

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This case-control study investigated the expression levels of miR-340, LGR5, and FOXO1 genes in ovarian cancer tissues and cisplatin-resistant versus sensitive cell lines to understand mechanisms of drug resistance. The researchers found that tumor tissues exhibited significantly higher LGR5 expression and lower miR-340 and FOXO1 expression compared to normal adjacent tissues. In vitro experiments demonstrated that cisplatin treatment altered these gene expressions differently in sensitive and resistant cell lines, suggesting their involvement in chemoresistance pathways. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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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 ± 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 ≤ 0.001), the LGR5 gene presented a significant increase in expression (p ≤ 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 ≤ 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.
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It can be concluded that the miR-340 , LGR5 , and FOXO1 genes can be targeted for safer treatment and preservation of reproductive ability in patients with ovarian cancer by prevention of oophorectomy and/or high prescription of chemotherapy drugs.

Coi Statement

The authors declare that they have no conflict of interest.

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