5-Hydroxymethylcytosine profiles in circulating cell-free DNA serve as potential biomarkers for diagnosis and classification of adenomyosis

Abstract

Background: At present, clinical diagnosis and classification of adenomyosis are mainly dependent on MRI or pathological examination, and little research is carried out on molecular biomarkers for the diagnosis and classification of adenomyosis. Our aim is to identify molecular biomarkers for the diagnosis and classification of adenomyosis. Methods: 5hmC-Seal technique was used to obtain genome-wide 5hmC profiles from plasma cfDNA and tissue genomic DNA samples. Patients were divided into the training (n = 26) and the validation group (n = 25), and a 5hmC-based Logistic regression model from the training group was developed to verify the diagnostic capability of the model. Meanwhile, we investigated whether 5hmC molecular markers could be used to classify the two main subtypes of adenomyosis. Results: In this study, ten 5hmC markers were identified by using machine learning techniques. The diagnostic ability reached 0.88 sensitivity and 0.87 specificity (AUC = 0.91). Next, we found that 5hmC markers can be used as markers for adenomyosis classification. Conclusions: Our results showed that 5hmC markers of cfDNA had the potential to be used for diagnosis and classification in adenomyosis patients, and 5hmC-Seal may be a clinically applicable and minimally invasive method for the diagnosis and classification of adenomyosis in the future.