The mass spectrometry-based molecular profiling can be used for better differentiation between normal and cancer tissues and for the detection of neoplastic transformation, which is of great importance for diagnostics of a pathology, prognosis of its evolution trend, and development of a treatment strategy. The aim of the present study is the evaluation of tissue classification approaches based on various data sets derived from the molecular profile of the organic solvent extracts of a tissue. A set of possibilities are considered for the orthogonal projections to latent structures discriminant analysis: all mass spectrometric peaks over 300 counts threshold, subset of peaks selected by ranking with support vector machine algorithm, peaks selected by random forest algorithm, peaks with the statistically significant difference of the intensity determined by the Mann-Whitney U test, peaks identified as lipids, and both identified and significantly different peaks. The best predictive potential is obtained for OPLS-DA model built on nonpolar glycerolipids (Q 2 = 0.64, area under curve [AUC] = 0.95); the second one is OPLS-DA model with lipid peaks selected by random forest algorithm (Q 2 = 0.58, AUC = 0.87). Moreover, models based on particular molecular classes are more preferable from biological point of view, resulting in new explanatory mechanisms of pathophysiology and providing a pathway analysis. Another promising features for OPLS-DA modeling are phosphatidylethanolamines (Q 2 = 0.48, AUC = 0.86). Journal of MASS SPECTROMETRY 4 | CONCLUSION ESI-MS shotgun lipidomics of a tissue takes about 25 minutes including sample preparation. It is somewhat faster than the common cervical cancer identification methods such as histology and can give significantly more information. Thus, it has a potential for precise and personalized characterization of cancer as a supplement for histological examination. Influence of pre-analytical experimental data processing on the classification model predictive potential is analyzed.The OPLS-DA model based on nonpolar glycerolipids demonstrated the best predictive power. These data sets together with ethanolamines are the most promising for tissue classification among the data bearing essential biochemical information.

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A dramatic increase in cervical diseases associated with human papillomaviruses (HPV) in women of reproductive age has been observed over the past decades. An accurate differential diagnosis of the severity of сervical intraepithelial neoplasia and the choice of the optimal treatment requires the search for effective biomarkers with high diagnostic and prognostic value. The objective of this study was to introduce a method for rapid shotgun lipidomics to differentiate stages of HPV-associated cervix epithelium transformation. Tissue samples from 110 HPV-positive women with cervicitis (n = 30), low-grade squamous intraepithelial lesions (LSIL) (n = 30), high-grade squamous intraepithelial lesions (HSIL) (n = 30), and cervical cancers (n = 20) were obtained. The cervical epithelial tissue lipidome at different stages of cervix neoplastic transformation was studied by a shotgun label-free approach. It is based on electrospray ionization mass spectrometry (ESI-MS) data of a tissue extract. Lipidomic data were processed by the orthogonal projections to latent structures discriminant analysis (OPLS-DA) to build statistical models, differentiating stages of cervix transformation. Significant differences in the lipid profile between the lesion and surrounding tissues were revealed in chronic cervicitis, LSIL, HSIL, and cervical cancer. The lipids specific for HPV-induced cervical transformation mainly belong to glycerophospholipids: phosphatidylcholines, and phosphatidylethanolamines. The developed diagnostic OPLS-DA models were based on 23 marker lipids. More than 90% of these marker lipids positively correlated with the degree of cervix transformation. The algorithm was developed for the management of patients with HPV-associated diseases of the cervix, based on the panel of 23 lipids as a result. ESI-MS analysis of a lipid extract by direct injection through a loop, takes about 25 min (including preparation of the lipid extract), which is significantly less than the time required for the HPV test (several hours for hybrid capture and about an hour for PCR). This makes lipid mass spectrometric analysis a promising method for express diagnostics of HPV-associated neoplastic diseases of the cervix.

Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. академика В.И. Кулакова; 117997, Россия, Москва, ул. Академика Опарина, д. 4 Резюме Среди гинекологических заболеваний у женщин репродуктивного возраста ведущее место занимают воспалительные заболевания нижнего отдела генитального тракта (70%), значительную долю которых составляют воспалительные процессы влагалища и шейки матки. У ⅔ женщин цервицит чаще всего протекает бессимптомно, поэтому они не обращаются за лечением, а у 65-77,6% отмечается переход в хроническую форму. Так, хронический цервицит диагностируется почти у каждой третьей женщины, обращающейся за помощью к гинекологу в связи с лейкореей, тенденции к снижению частоты заболевания не отмечается. В статье представлен актуальный взгляд на проблему воспалительных заболеваний нижнего отдела полового тракта. Проведен анализ ряда исследований, посвященных влиянию локального иммунитета и состояния микрофлоры влагалища на развитие хронических воспалительных заболеваний. Представлены результаты протеомных исследований цервиковагинальной жидкости в ранней диагностике воспалительных заболеваний нижнего отдела полового тракта и возможность использования цитокиновых биомаркеров в клинической практике с целью прогнозирования патологического состояния и выбора дальнейшей тактики лечения пациентки. Рассмотрена эффективность использования комбинированного препарата на основе хлоргексидина и декспантенола, обладающего выраженным противомикробным, регенерирующим и метаболическим действием и применяемым в терапии острых и хронических вагинитов; бактериального вагиноза; эндо-, экзоцервицитов, что является актуальным в терапии воспалительных заболеваний нижнего отдела генитального тракта.Ключевые слова: вагинит, цервицит, хлоргексидин, декспантенол, лейкорея Для цитирования: Назарова Н.М., Некрасова М.Е., Довлетханова Э.Р., Абакарова П.Р. Вагиниты и цервициты: выбор эффективного метода терапии (обзор литературы). Медицинский совет. 2020;(3):17-23. AbstractAmong gynaecological diseases in women of reproductive age the leading place is occupied by inflammatory diseases of the lower part of the genital tract (70%), a significant proportion of which are inflammatory processes of the vagina and cervix uteri. In ⅔ of women, cervicitis is most often asymptomatic, so they do not seek medical treatment, and 65-77.6% have a transition to a chronic form. Thus, chronic cervicitis is diagnosed in almost one in three women who seek assistance from a gynaecologist due to leukorrhea, and there is no tendency for a decrease in frequency. The article presents an actual view on the problem of inflammatory diseases of the lower genital tract. The analysis of some researches devoted to the influence of local immunity and the state of vaginal microflora on the development of chronic inflammatory diseases is carried out. The results of proteomic researches of cervicovaginal fluid in early diagnostics of inflammatory diseases of the lower genital tract and the possibility of using cytokine biomarkers i...

HPV infects epithelial tissues regardless of their location and penetrates into the cell through microscopic cuts. The clinical manifestations of HPV-associated diseases are diverse and equally relevant for women and men. Despite the fact that exophytic condylomas are regarded as a benign disease and establishing diagnosis does not cause difficulties, a clinician should always have oncological alertness, especially with regard to diffuse, long-lasting condylomatosis.