MicroRNAs as surrogate biomarkers of future endometrial malignancy in women with endometrial hyperplasia without atypia and an open-label randomized trial of metformin, weight control, and exercise intervention.

Abstract

5622 Background: Endometrial hyperplasia (EH) is regarded as an endometrial cancer (EC) precursor. The severity of atypia reflects risk of future EC. According to Kurman et al., the risk of progression to EC was < 1% in simple hyperplasia (SH) and 3% in complex hyperplasia (CH) without atypia (non-A). Our group previously identified 4 MicroRNAs (MiRs) and PTEN by immunohistochemistry stain are significant risk biomarkers of future endometrial malignancy. Methods: This prospective open-label randomized controlled study enrolled a total of 60 patients SH/CH non-A. All participants were randomized 1:1 to with or without metformin intervention and received education for exercise and weight control. A stratification of body mass index was performed, but not for HbA1C. PTEN immunohistochemistry stain and MiR profiles of the endometrial tissue were analyzed. Results: 57 participants were eligible for analysis. After all the participants had been followed up for 3 years, an analysis was performed in which 3 with progression to atypical hyperplasia and 6 with recurrent SH/CH non-A were observed. Exercise intensity was inversely correlated with use of metformin or not (p = 0.028). The predicting progression/recurrence by any of the 4 miRs (miR30a-3p, miR141, miR-200a, and miR200b) were all significant (p < 0.05). PTEN expression, metformin, exercise, or body weight control intervention did not alter the risk of EH recurrence/EC progression. Metformin group has a trend of decreased risk of progression/recurrence yet not significant (p = 0.291). The decreased impact of metformin may be partly related to their lower intensity of exercise as compared to no-metformin group. Impact of interventions may need longer observation. Conclusions: Presence of any of the 4 miRs (miR30a-3p, miR141, miR-200a, and miR200b) seem related to risk of recurrence/progression of SH/CH non-A, while PTEN expression, metformin, exercise, and weight control are not, in our prospective cohort. Clinical trial information: NCT05292573 .