[Prognostic ability of seminal plasma lipidomic analysis in predicting the success of microTESE in men with azoospermia].

INTRODUCTION: The aim of this work is to assess the possibility of metabolomic (specifically lipidomic) analysis of seminal plasma to identify patients with preserved focal spermatogenesis in the testes who may have a reasonable chance of sperm retrieval during the microTESE procedure. MATERIALS AND METHODS: lipid composition of semen plasma samples from 64 men with azoospermia and 24 fertile control men was analyzed. Lipids were isolated from semen by a modified Folch extraction method. Lipid extracts were analyzed by reverse phase liquid chromatography coupled to mass spectrometry. Lipidomic data were compared with the results of the microTESE procedure. RESULTS: Comparison of two groups revealed a statistically significant difference in concentration for 23 lipids detected in positive ion mode and 37 lipids detected in negative ion mode. Those lipids mainly belong to hexosylceramides, sphingomyelins and phosphatidylcholines, phosphatidylethanolamines and their ethers. In multivariate analysis content of SM d16: 1/18:0 lipid (beta coefficient: -7.23; 95% confidence interval [95% CI]: -11.93 to - 2.53; odds ratio: 7.23e-04; CI for odds ratio: 6.59e-06 to 7.93e-02; Walds test: -3.02; p=0.003), content of TG 14: 1_16 : 0_18: 3 lipid (beta 2.95; 95% CI 0.98 to 4.93; odds ratio: 1.92e + 01; CI for odds ratio: 2.66e + 00 to 1.39e + 02 ; Walds test: 2.93; p=0.003) and testicular volume (beta: 0.14; 95% CI: 0.04 to 2.45; odds ratio: 1.15e + 00; CI odds ratio: from 1.04e + 00 to 1.27e + 00; Walds test: 2.65; p=0.008) were significantly associated with positive MicroTESE outcome. The sensitivity of this regression model was 61%, the specificity was 83%, and the AUC was 0.75. CONCLUSIONS: seminal plasma serves as a rich source of biological markers for identifying patients with preserved focal spermatogenesis in the testes. Seminal plasma lipidomic profile of the of patients in the control group with normal spermatogenesis clearly differs from the profile of patients with azoospermia, also there was a significant difference in content of a difference in lipids between patients with positive and negative microTESE outcomes. These are preliminary results and further research is needed to confirm the validity of the resulting lipid panel.

[Lipidomic markers of tumor progress in breast cancer patients]. / Lipidomnye markery opukholevoi progressii u bol'nykh rakom molochnoi zhelezy.

Research of cancer progression mechanisms and their impact on metabolism of tumor cells and tumor microenvironment cells is an important element in drug development for cancer target therapy. In this study, changes in tumor tissue and margin tissue lipid profiles, were associated with the following clinical and morphological characteristics: tumor size, cancer stage, multifocalite, tumor grade, number of lymph node metastasis, Nottingham prognostic index, total malignancy score, level of Ki67 protein. Lipid profiling was performed by reverse-phase chromato-mass spectrometry analysis of lipid tissue extract with lipid identification by characteristic fragments. In the lipid profile of tumor tissue 13 characteristic lipids were selected. Their levels significantly correlated with at least 5 clinical and morphological features. Eight of 13 belonged to phosphatidylcholines. In lipid profile of tumor microenviroment tissue 13 lipid features were selected. Their levels significantly correlated with at least 5 clinical and morphological features. Four of 13 belonged to oxidized lipids, 4 lipid features belonged to sphingomyelins, four of 13 belonged to phosphatidylethanolamines. The tumor microenvironment tissue lipid profile correlated with tumor size, cancer stage, tumor grade, number of axillary metastases, Nottingham prognostic index. The tumor tissue lipid profile correlated with tumor size, tumor grade, total malignant score, and number of axillary metastases.

[Lipidomic markers of breast cancer malignant tumor histological types]. / Lipidomnye markery gistologicheskikh tipov zlokachestvennoi opukholi molochnoi zhelezy.

The molecular profile of a tumor is associated with its histological type and can be used both to study the mechanisms of tumor progression and to diagnose it. In this work, changes in the lipid profile of a malignant breast tumor and the adjacent tissue were studied. The potential possibility of determining the histological type of the tumor by its lipid profile was evaluated. Lipid profiling was performed by reverse-phase chromato-mass-spectrometric analysis the tissue of lipid extract with identification of lipids by characteristic fragments. Potential lipid markers of the histological type of tumor were determined using the Kruskal-Wallis test. Impact of lipid markers was calculated by MetaboAnalyst. Classification models were built by support vector machines with linear kernel and 1-vs-1 architecture. Models were validated by leave-one out cross-validation. Accuracy of models based on microenvironment tissue, were 99% and 75%, accuracy of models, based on tumor tissue, were 90% and 40% for the positive ion mode and negative ion mode respectively. The lipid profile of marginal (adjacent) tissue can be used for identification histological types of breast cancer. Glycerophospholipid metabolism pathway changes were statistically significant in the adjacent tissue and tumor tissue.

Lipid Alterations in Early-Stage High-Grade Serous Ovarian Cancer.

Epithelial ovarian cancer (OC) ranks first in the number of deaths among diseases of the female reproductive organs. Identification of OC at early stages is highly beneficial for the treatment but is highly challenging due to the asymptomatic or low-symptom disease development. In this study, lipid extracts of venous blood samples from 41 female volunteers, including 28 therapy-naive patients with histologically verified high-grade serous ovarian cancer at different stages (5 patients with I-II stages; 23 patients with III-IV stages) and 13 apparently healthy women of reproductive age, were profiled by high-performance liquid chromatography mass spectrometry (HPLC-MS). Based on MS signals of 128 differential lipid species with statistically significant level variation between the OC patients and control group, an OPLS-DA model was developed for the recognition of OC with 100% sensitivity and specificity R 2 = 0.87 and Q2 = 0.80. The second OPLS-DA model was developed for the differentiation between I-II OC stages and control group with R 2 = 0.97 and Q2 = 0.86 based on the signal levels of 108 differential lipid species. The third OPLS-DA model was developed for the differentiation between I-II OC stages and III-IV stages based on the signal levels of 99 differential lipid species. Various lipid classes (diglycerides, triglycerides, phosphatidylchlorines, ethanolamines, sphingomyelins, ceramides, phosphatidylcholines and phosphoinositols) in blood plasma samples display distinctly characteristic profiles in I-II OC, which indicates the possibility of their use as marker oncolipids in diagnostic molecular panels of early OC stages. Our results suggest that lipid profiling by HPLC-MS can improve identification of early-stage OC and thus increase the efficiency of treatment.

Exhaled breath condensate analysis from intubated newborns by nano-HPLC coupled to high resolution MS.

Invasiveness of examination and therapy methods is a serious problem for intensive care and nursing of premature infants. Exhaled breath condensate (EBC) is the most attractive biofluid for non-invasive methods development in neonatology for monitoring the status of intubated infants. The aim of the study was to propose an approach for EBC sampling and analysis from mechanically ventilated neonates. EBC collection system with good reproducibility of sampling was demonstrated. Discovery-based proteomic and metabolomic studies were performed using nano-HPLC coupled to high resolution MS. Label-free semi-quantitative data were compared for intubated neonates with congenital pneumonia (12 infants) and left-sided congenital diaphragmatic hernia (12 infants) in order to define disease-specific features. Totally 119 proteins and 164 metabolites were found. A number of proteins and metabolites that can act as potential biomarkers of respiratory diseases were proposed and require further validation.