Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed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

How to cite: Krasnyi, A.M.; Gadzhieva, L.T.; Kokoeva, D.N.; Kosenko, M.G.; Yarotskaya, E.L.; Pavlovich, S.V.; Ashrafyan, L.A.; Sukhikh, G. Analysis of CDO, PITX2, and CDH13 gene methylation in early endometrial cancer for prediction of medical treatment outcomes. Preprints 2024, 2024021464. https://doi.org/10.20944/preprints202402.1464.v1 Krasnyi, A.M.; Gadzhieva, L.T.; Kokoeva, D.N.; Kosenko, M.G.; Yarotskaya, E.L.; Pavlovich, S.V.; Ashrafyan, L.A.; Sukhikh, G. Analysis of CDO, PITX2, and CDH13 gene methylation in early endometrial cancer for prediction of medical treatment outcomes. Preprints 2024, 2024021464. https://doi.org/10.20944/preprints202402.1464.v1

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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