Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Analysis of CDO, PITX2, and CDH13 gene methylation in early endometrial cancer for prediction of medical treatment outcomes

Version 1 : Received: 26 February 2024 / Approved: 26 February 2024 / Online: 26 February 2024 (14:19:49 CET)

A peer-reviewed article of this Preprint also exists.

Krasnyi, A.M.; Gadzhieva, L.T.; Kokoeva, D.N.; Kosenko, M.G.; Yarotskaya, E.L.; Pavlovich, S.V.; Ashrafyan, L.A.; Sukhikh, G.T. Analysis of CDO1, PITX2, and CDH13 Gene Methylation in Early Endometrial Cancer for Prediction of Medical Treatment Outcomes. Int. J. Mol. Sci. 2024, 25, 4892. Krasnyi, A.M.; Gadzhieva, L.T.; Kokoeva, D.N.; Kosenko, M.G.; Yarotskaya, E.L.; Pavlovich, S.V.; Ashrafyan, L.A.; Sukhikh, G.T. Analysis of CDO1, PITX2, and CDH13 Gene Methylation in Early Endometrial Cancer for Prediction of Medical Treatment Outcomes. Int. J. Mol. Sci. 2024, 25, 4892.

Abstract

An observational cohort study of patients diagnosed with endometrial cancer (EC) stage IA G1, or atypical endometrial hyperplasia (AHE), undergoing organ-preserving treatment, was conducted. Objective of the study: to determine CDO1, PITX2, and CDH13 gene methylation levels in early endometrial cancer and atypical hyperplasia specimens obtained before organ-preserving treatment in the patients with adequate response and with insufficient response to hormonal treatment. Materials and methods: 41 endometrial specimens obtained during diagnostic uterine curettage in women with EC (n=28) and AEH (n=13), willing to preserve reproductive function, were studied; 18 specimens of endometrial cancer IA stage G1 from peri- and early postmenopausal women (comparison group) were included in the study. The control group included 18 endometrial specimens from healthy women obtained by diagnostic curettage for missed abortion and/or intrauterine adhesions. Methylation levels were analyzed using the modified MS-HRM method. Results: All 13 women with AEH had complete response (CR) to medical treatment. In the group undergoing organ-preserving treatment for uterine cancer IA stage G1 (n=28), 14 patients had complete response (EC CR group) and 14 had not (non-CR). It was found that all groups had statistically significant differences in CDO1 gene methylation levels with the control group (p<0.001) except for the EC CR group (p=0.21). The p-value of difference between EC CR and EC non-CR groups was <0.001. The differences in PITX2 gene methylation levels between the control and study groups were also significantly different (p<0.001), except for AEH group (p=0.21). For the difference between EC CR and EC non-CR groups, the p-value was 0.43. For CDH13 gene methylation levels, statistically significant differences were found between the control and EC non-CR groups (p<0.001), and the control and EC comparison groups (p=0.005). When comparing the EC CR group with EC non-CR group, the p-value for this gene was <0.001. Simultaneous assessment of CDO1 and CDH13 genes methylation allowed to accurately distinguish between EC CR and EC non-CR groups (AUC=0.96). Conclusion: Assessment of CDO1 and CDH13 gene methylation in endometrial specimens from patients with endometrial cancer (IA stage G1), planned for medical treatment, can predict the treatment outcome.

Keywords

methylation; atypical endometrial hyperplasia; endometrial cancer; organ-preserving treatment; MS-HRM; CDO1; CDH13

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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