Shedding Light on Ovarian Cancer: MicroRNA-590 and FOXA2 as Novel Diagnostic Signatures
Abstract
In recent years, there has been a lot of interest in the study for particular biomarkers in ovarian cancer. By targeting tumor suppressors, microRNA-590 has been shown to increase the proliferation of ovarian cancer cells and plays a significant role in the formation of tumors. Numerous cancers, including ovarian cancer, have decreased expression of the tumor suppressor transcription factor FOXA2. The purpose of this study was to assess the diagnostic value of circulating MicroRNA-590 and FOXA2 levels in patients with ovarian cancer. A case-control study comprising 35 healthy controls and 70 ovarian cancer patients was carried out. ELISA was used to measure the levels of FOXA2 in the serum. Using qRT-PCR, the amount of circulating MicroRNA-590 was measured. The 2^-ΔΔCt technique was used to calculate fold change values. ROC curve and logistic regression were used in statistical analysis to compare groups and assess diagnostic value. Compared to controls, ovarian cancer patients had significantly reduced levels of FOXA2 and MicroRNA-590 expression. MicroRNA-590 fold change values were found to have significantly decreased. MicroRNA-590 had an efficient diagnostic value (AUC = 84.5%), according to ROC curve analysis, whereas FOXA2 had limited diagnostic performance. Both indicators' diagnostic significance was validated using logistic regression. MicroRNA-590 and circulating FOXA2 levels are decreased in ovarian cancer and could be useful non-invasive diagnostic indicators. Superior diagnostic accuracy was demonstrated by MicroRNA-590, which may help in early diagnosis and differentiation from healthy individuals.
References
A. De Leo et al., “What is new on ovarian carcinoma: Integrated morphologic and molecular analysis following the new 2020 World Health Organization classification of female genital tumors,” Diagnostics, vol. 11, no. 4, p. 697, 2021. [Online]. Available: https://doi.org/10.3390/diagnostics11040697
H. Moch, WHO Classification of Tumours. Volume 4: Female genital tumours. Geneva, Switzerland: World Health Organization, 2020.
S. Nag, A. Aggarwal, A. Rauthan, and S. Warrier, “Maintenance therapy for newly diagnosed epithelial ovarian cancer—A review,” J. Ovarian Res., vol. 15, p. 88, 2022. [Online]. Available: https://doi.org/10.1186/s13048-022-00975-9
P. DiSilvestro and A. A. Secord, “Maintenance treatment of recurrent ovarian cancer: Is it ready for prime time?,” Cancer Treat. Rev., vol. 69, pp. 53–65, 2018. [Online]. Available: https://doi.org/10.1016/j.ctrv.2018.06.005
S. G. Silverberg, “Histopathologic grading of ovarian carcinoma: A review and proposal,” Int. J. Gynecol. Pathol., vol. 19, no. 1, pp. 7–15, 2000. [Online]. Available: https://doi.org/10.1097/00004347-200001000-00002
P. Barnard et al., “Inter-pathologist and pathology report agreement for ovarian tumor characteristics in the Nurses’ Health Studies,” Gynecol. Oncol., vol. 150, no. 3, pp. 521–526, 2018. [Online]. Available: https://doi.org/10.1016/j.ygyno.2018.07.002
S. Lin and R. I. Gregory, “MicroRNA biogenesis pathways in cancer,” Nat. Rev. Cancer, vol. 15, pp. 321–333, 2015. [Online]. Available: https://doi.org/10.1038/nrc3932
A. Eulalio et al., “Functional screening identifies miRNAs inducing cardiac regeneration,” Nature, vol. 492, pp. 376–381, 2012. [Online]. Available: https://doi.org/10.1038/nature11739
M. H. Miao et al., “miR-590 promotes cell proliferation and invasion in T-cell acute lymphoblastic leukaemia by inhibiting RB1,” Oncotarget, vol. 7, no. 26, pp. 39527–39534, 2016. [Online]. Available: https://doi.org/10.18632/oncotarget.9685
M. Salem et al., “miR-590-3p targets cyclin G2 and FOXO3 to promote ovarian cancer cell proliferation, invasion, and spheroid formation,” Int. J. Mol. Sci., vol. 20, no. 7, p. 1810, 2019. [Online]. Available: https://doi.org/10.3390/ijms20071810
G. A. Atallah et al., “New predictive biomarkers for ovarian cancer,” Diagnostics, vol. 11, no. 3, p. 465, 2021. [Online]. Available: https://doi.org/10.3390/diagnostics11030465
J. Li, W. Shao, and H. Feng, “MiR-542-3p, a microRNA targeting CDK14, suppresses cell proliferation, invasiveness, and tumorigenesis of epithelial ovarian cancer,” Biomed. Pharmacother., vol. 110, pp. 850–856, 2019. [Online]. Available: https://doi.org/10.1016/j.biopha.2018.12.080
M. Fu et al., “Forkhead box family transcription factors as versatile regulators for cellular reprogramming to pluripotency,” Cell Regen., vol. 10, p. 17, 2021. [Online]. Available: https://doi.org/10.1186/s13619-021-00076-5
C. Vorvis et al., “Transcriptomic and CRISPR/Cas9 technologies reveal FOXA2 as a tumor suppressor gene in pancreatic cancer,” Am. J. Physiol. Gastrointest. Liver Physiol., vol. 310, no. 12, pp. G1124–G1137, 2016. [Online]. Available: https://doi.org/10.1152/ajpgi.00389.2015
C. M. C. Li et al., “Foxa2 and Cdx2 cooperate with Nkx2–1 to inhibit lung adenocarcinoma metastasis,” Genes Dev., vol. 29, no. 18, pp. 1850–1862, 2015. [Online]. Available: https://doi.org/10.1101/gad.263384.115
Q. Sun, X. Lei, and X. Yang, “The crosstalk between non-coding RNAs and oxidative stress in cancer progression,” Genes Dis., vol. 12, no. 3, art. 101286, 2025. [Online]. Available: https://doi.org/10.1016/j.gendis.2023.101286
K. J. Livak and T. D. Schmittgen, “Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method,” Methods, vol. 25, no. 4, pp. 402–408, 2001. [Online]. Available: https://doi.org/10.1006/meth.2001.1262
M. Salem et al., “miR-590-3p promotes ovarian cancer growth and metastasis via a novel FOXA2-versican pathway,” Cancer Res., vol. 78, no. 15, pp. 4175–4190, 2018. [Online]. Available: https://doi.org/10.1158/0008-5472.CAN-18-0451
Copyright (c) 2025 Zahraa Abdulkadhim Saddam, Rana Majeed Hameed, Zahraa Sabbar Omran
This work is licensed under a Creative Commons Attribution 4.0 International License.
