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Abstract INTRODUCTION: Uterine leiomyoma is one of the most frequent gynecological pathologies in women before the menopause. Despite numerous studies of factors involved in the genesis and growth of uterine leiomyomas the causes of uterine fibroids, as well as its recurrence are still the subject of discussion. It is of great interest to develop new noninvasive methods of early diagnosis of uterine leiomyomas and its recurrences using highly informative modern techniques such as mass spectrometry. Early prediction of leiomyoma recurrence will assist the patient and her gynecologist in deciding the most appropriate method of treatment.
METHOD: The study included 35 women with newly diagnosed uterine leiomyomas and 31 women diagnosed with recurrent uterine leiomyomas, who were examined and operated in the Department of a Gynecologic Surgery at V. I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology. Uterine fibroids were diagnosed by vaginal examination, ultrasound data, confirmed laparoscopically, and finally verified histologically. Lipid composition of samples was determined by LC- MS/MS analysis using Maxis Impact qTOF mass spectrometer. Multivariate data analysis of the MS data was performed with principal components analysis (PCA) to detect outliers, and partial least squares-discriminant analysis (PLS-DA) with Pareto scaling using “ropls” library to find out if the MS data was sufficient for the classification of samples under the study.
RESULTS: Blood plasma from 66 women with leiomyomas and 15 women of control group were investigated by the ESI-MS method to obtain information about molecular composition. Among all detected metabolites, 267 significant lipid peaks were identified and divided into five different classes: phosphatidylcholines, phosphatidylethanolamines, sphingomyelins, di- and triglycerides. The identification was provided according to accurate mass within 10 ppm mass accuracy. MS/MS information about the fragmentation pattern was used for better peak assignment. Based on semi-quantitative data on the level of potential lipid biomarkers in the blood plasma, OPLS-DA models were developed to classify patients. Analysis of plasma lipid composition in patients with leiomyoma and leiomyoma recurrences, and patients without uterine fibroids revealed a number of phospholipids, sphingomyelins, cholesterol esters and triglycerides, the levels of which differ significantly in blood plasma. The lipids test panel was suggested for early diagnosis of uterus leiomyoma recurrences.
CONCLUSION: A comparative study of the mass spectrometric profiles of blood plasma allows us to identify new molecular markers for early diagnosis of uterus leiomyoma recurrences. In the future, the results of our research will be used to determine the optimal treatment strategy for patients with uterine leiomyoma, and will lead to the creation of new prognostic strategies and therapies.
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= Discovery stage.
= Translation stage.
= Clinically available.
