TP63-TRIM29 axis regulates enhancer methylation and chromosomal instability in prostate cancer.

BACKGROUND: Prostate adenocarcinoma (PRAD) is the second leading cause of cancer-related deaths in men. High variability in DNA methylation and a high rate of large genomic rearrangements are often observed in PRAD. RESULTS: To investigate the reasons for such high variance, we integrated DNA methylation, RNA-seq, and copy number alterations datasets from The Cancer Genome Atlas (TCGA), focusing on PRAD, and employed weighted gene co-expression network analysis (WGCNA). Our results show that only single cluster of co-expressed genes is associated with genomic and epigenomic instability. Within this cluster, TP63 and TRIM29 are key transcription regulators and are downregulated in PRAD. We discovered that TP63 regulates the level of enhancer methylation in prostate basal epithelial cells. TRIM29 forms a complex with TP63 and together regulates the expression of genes specific to the prostate basal epithelium. In addition, TRIM29 binds DNA repair proteins and prevents the formation of the TMPRSS2:ERG gene fusion typically observed in PRAD. CONCLUSION: Our study demonstrates that TRIM29 and TP63 are important regulators in maintaining the identity of the basal epithelium under physiological conditions. Furthermore, we uncover the role of TRIM29 in PRAD development.

[Surgical and combined treatment of patients with craniovertebral junction meningioma: a single-center retrospective study of 196 cases]. / Analiz rezul'tatov khirurgicheskogo i kombinirovannogo lecheniya patsientov s meningiomami oblasti kraniovertebral'nogo perekhoda: odnotsentrovoe retrospektivnoe issledovanie 196 sluchaev.

Treatment of craniovertebral junction meningioma is a difficult task. Surgical treatment is the gold standard for these patients. However, it is associated with high risk of neurological impairment, while combined treatment (surgery + radiotherapy) provides more favorable outcomes. OBJECTIVE: To present the results of surgical and combined treatment of patients with craniovertebral junction meningioma. MATERIAL AND METHODS: There were 196 patients with craniovertebral junction meningioma who underwent surgical or combined (surgery + radiotherapy) treatment at the Burdenko Neurosurgery Center between January 2005 and June 2022. The sample included 151 women and 45 men (3.4:1). Resection of tumor was performed in 97.4% of patients, craniovertebral junction decompression with dural defect closure - 2%, ventriculoperitoneostomy - 0.5%. As the second stage, 40 patients (20.4%) underwent radiotherapy. RESULTS: Total resection was achieved in 106 patients (55.2%), subtotal - 63 (32.8%), partial - 20 (10.4%), tumor biopsy was performed in 3 (1.6%) cases. Intraoperative complications occurred in 8 patients (4%), postoperative complications - in 19 (9.7%) cases. Radiosurgery was carried out in 6 (15%) patients, hypofractionated irradiation - 15 (37.5%), standard fractionation - 19 (47.5%) patients. Tumor growth control after combined treatment made up 84%. CONCLUSION: Clinical outcomes in patients with craniovertebral junction meningioma depend on tumor dimensions, topographic and anatomical localization of tumor, resection quality and relationship with surrounding structures. Combined treatment of anterior and anterolateral meningiomas of the craniovertebral junction is preferable compared to total resection.

Carotid Enadrterectomy for Thrombosis of the Internal Carotid Artery in Patients With COVID-19.

Analysis of the results of emergency carotid endarterectomy (CEE) against the background of internal carotid artery (ICA) thrombosis in the acute period of acute cerebrovascular accident (ACVA) in patients with COVID-19. During the COVID-19 pandemic (April 1, 2020-May 1, 2021), 43 patients with ICA thrombosis and a positive polymerase chain reaction (PCR) result for SARS-CoV-2 were included in this prospective study. In all cases, CEE was performed in the acutest period of ACVA. These patients were included in group 1. The comparison group was represented by 89 patients who underwent CEE in the acute period of stroke, in the period before the COVID-19 pandemic (April 1, 2019-March 1, 2020). According to laboratory parameters, patients with COVID-19 had severe coagulopathy (with an increase in D-dimer: 3832 ± 627.2 ng/mL, fibrinogen: 12.6 ± 3.1 g/L, prothrombin: 155.7 ± 10, 2%), inflammatory syndrome (increased ferritin: 646.2 ± 56.1 ng/mL, C-reactive protein: 161.3 ± 17.2 mg/L, interleukin-6: 183.3 ± 51.7 pg/mL, leukocytosis: 27.3 ± 1.7 10E9/L). In the hospital postoperative period, the groups were comparable in terms of the incidence of deaths (group 1: 2.3%, n = 1; group 2: 1.1%, n = 1; P= 0.81; OR=2.09; 95 % CI = 0.12-34.3) myocardial infarction (group 1: 2.3%, n = 1; group 2: 0%; P= 0.7; OR = 6.3; 95% CI = 0.25-158.5), CVA (group 1: 2.3%, n = 1; group 2: 2.2%, n = 2; P= 0.55; OR = 1.03; 95% CI = 0,.09-11.7). ICA thrombosis and hemorrhagic transformations were not recorded. However, due to severe coagulopathy with ongoing anticoagulant/antiplatelet therapy, patients with COVID-19 more often developed bleeding in the operation area (group 1: 11.6%, n = 5; group 2: 1.1%, n = 1; P= 0.02; OR = 11.5; 95% CI = 1.3-102.5). In all cases, the flow of hemorrhagic discharge came from the drainage localized in the subcutaneous fat. This made it possible to remove skin sutures in a dressing room, suturing the source of bleeding and applying secondary sutures under local anesthesia. Emergency CEE in the acute period of stroke is an effective and safe method of cerebral revascularization in case of ICA thrombosis in conditions of COVID-19.

[The DNA methylation profiling in the study and treatment of patients with meningiomas of the craniovertebral junction]. / Znachenie analiza metilirovaniya DNK v issledovanii i lechenii patsientov s meningiomami oblasti kraniovertebral'nogo perekhoda.

The paper presents the experience of using DNA methylation status in patients with meningiomas of the craniovertebral junction area in a neurosurgical clinic. A clinical case of combined treatment of a patient with meningioma of the craniovertebral junction and the choice of tactics based on the result of DNA methylation analysis of meningioma are described.

CAROTIDSCORE.RU-The first Russian computer program for risk stratification of postoperative complications of carotid endarterectomy.

GOAL: Presentation of the first Russian computer program (www.carotidscore.ru) for risk stratification of postoperative complications of carotid endarterectomy (CEE). MATERIAL AND METHODS: The present study is based on the analysis of a multicenter Russian database that includes 25,812 patients after CEE operated on from 01/01/2010 to 04/01/2022. The following types of CEE were implemented: 6814 classical CEE with plastic reconstruction of the reconstruction zone with a patch; 18,998 eversion CEE. RESULTS: In the hospital postoperative period, 0.18% developed a lethal outcome, 0.14%-myocardial infarction, 0.35%-stroke. The combined endpoint was 0.68%. For each factor present in patients, a predictive coefficient was calculated. The prognostic coefficient was a numerical indicator reflecting the strength of the influence of each factor on the development of postoperative complications. Based on this formula, predictive coefficients were calculated for each factor present in patients in our study. The total contribution of these factors was reflected in "%" and denoted the risk of postoperative complications with a minimum value of 0% and a maximum of 100%. On the basis of the obtained calculations, a computer program CarotidSCORE was created. Its graphical interface is based on the QT framework (https://www.qt.io), which has established itself as one of the best solutions for desktop applications. It is possible not only to calculate the probability of developing a complication, but also to save all data about the patient in JSON format (for the patient's personal card and his anamnesis). The CarotidSCORE program contains 47 patient parameters, including clinical-demographic, anamnestic and angiographic characteristics. It allows you to choose one of the four types of CEE, which will provide an accurate stratification of the risk of complications for each of them in person. CONCLUSION: CarotidSCORE (www.carotidscore.ru) is able to determine the likelihood of postoperative complications in patients undergoing CEE.

[Long-term results of carotid endarterectomy and carotid artery stenting in patients with high bifurcation of common carotid artery: a multiple-center study]. / Otdalennye rezul'taty karotidnoi endarterektomii i karotidnoi angioplastiki so stentirovaniem u patsientov s vysokim raspolozheniem bifurkatsii obshchei sonnoi arterii. Rezul'taty mnogotsentrovogo issledovaniya.

OBJECTIVE: To analyze in-hospital and long-term results of eversion carotid endarterectomy (CEE), carotid endarterectomy with patch repair and carotid artery stenting (CAS) in patients with high bifurcation of common carotid artery. MATERIAL AND METHODS: A retrospective multiple-center open study included 1983 patients who underwent internal carotid artery (ICA) repair for severe stenosis between 2010 and 2021. Three groups of patients were distinguished depending on revascularization option: group 1 (n=638) - eversion CEE; group 2 (n=351) - CEE with patch repair; group 3 (n=994) - CAS. RESULTS: In-hospital postoperative mortality and incidence of stroke and myocardial infarction were similar. All bleedings (n=39) occurred after CEE. ICA thrombosis was diagnosed in groups 1 and 2 due to intimal detachment after insertion of temporary bypass tube. Incidence of laryngeal paresis, neuropathy of hypoglossal and glossopharyngeal nerves, Horner syndrome, damage to salivary glands was comparable in groups 1 and 2. Long-term mortality was the highest (n=10; 2.8%) after CEE with patch repair due to fatal stroke. In turn, the highest incidence of ICA restenosis and restenosis-induced ischemic stroke was observed after CEE with patch repair and CAS. CONCLUSION: 1. Classical and eversion CEE in patients with high CCA bifurcation is followed by high in-hospital incidence of damage to cranial nerves and salivary glands, laryngeal paresis, Horner syndrome, bleeding and risk of ICA thrombosis. 2. In patients with high CCA bifurcation, CAS and CEE with patch repair are accompanied by high incidence of ICA restenosis, restenosis-induced stroke and mortality in long-term postoperative period. 3. Eversion CEE demonstrates the lowest rates of all adverse cardiovascular events in long-term follow-up period.

[A multicenter study on the influence of different kinds of carotidal endarterectomy on the course of resistant arterial hypertension]. / Mnogotsentrovoe issledovanie vliyaniya razlichnykh vidov karotidnoi endarterektomii na techenie rezistentnoi arterial'noi gipertenzii.

OBJECTIVE: To analyze the dynamics of systolic blood pressure (SBP) and the results of various types of carotid endarterectomy (CEE) in patients with resistant arterial hypertension (RAH). MATERIALS AND METHODS: The study included 1577 patients with hemodynamically significant stenosis of the internal carotid artery (ICA) and RAH for more than 3 years. Patients were enrolled from January 2014 to December 2020. Depending on the implemented revascularization strategy, 5 groups were formed: group 1 (n=289 (18.3%)) with classical CEE with plasty of the reconstruction zone with a patch, group 2 (n=472 (29.9%)) with eversional CEE with cut-off of carotid glomus (CG); group 3 (n=109 (6.9%)) with the formation of a new bifurcation; group 4: (n=117 (7.4%)) with autoarterial reconstruction; group 5: (n=590 (37.4%)) with glomus-saving CEE. RESULTS: In the postoperative period, no significant differences were obtained in the frequency of deaths (0.34% for group 1; 0.63% for group 2; 0% for groups 3, 4 and 5), myocardial infarction (0.34%, 0.84%, 1.83, 0.85%, 0.33%, respectively); ischemic stroke (0.34%, 1.27%, 0.91%, 0.85%, 0.17%, respectively), hemorrhagic transformation (0%, 0.84%, 0.91%, 0.85%, 0%, respectively). However, according to the frequency of the combined endpoint (death + myocardial infarction + ischemic stroke + hemorrhagic transformation), the lowest rates were observed in the group of classical carotid endarterectomy with plasty of the reconstruction zone with a patch and glomus-sparing CEE (1.03%, 3.6%, 3.67%, 2.56%, 0.5%, respectively). This is due to the absence of cases of labile AH and hypertensive crises among patients of groups 1 and 5, which was ensured by the preservation of carotid glomus (CG). As a result, the number of patients with 2 and 3 degrees of hypertension in these groups decreased statistically significantly. The vast majority of patients after these operations achieved a stable target SBP. In groups 2, 3, and 4, there was a statistically significant increase in the number of patients with 2 and 3 degrees of AH, which is associated with excision of the CG. CONCLUSION: Classical CEE and glomus-sparing CEE techniques make it possible to achieve a stable target SBP level in patients with RAH as a result of CG preservation. Removal or traumatization of the latter during eversional CEE, the formation of a new bifurcation, autoarterial reconstruction is accompanied by the development of labile hypertension, an increase in the degree of hypertension and a high risk of hemorrhagic transformation in the brain. Thus, the most effective and safe types of CEE in the presence of RAH are classical CEE with plasty of the reconstruction zone with a patch and glomus-sparing CEE.

DNA methylation across the genome in aged human skeletal muscle tissue and muscle-derived cells: the role of HOX genes and physical activity.

Skeletal muscle tissue demonstrates global hypermethylation with age. However, methylome changes across the time-course of differentiation in aged human muscle derived cells, and larger coverage arrays in aged muscle tissue have not been undertaken. Using 850K DNA methylation arrays we compared the methylomes of young (27 ± 4.4 years) and aged (83 ± 4 years) human skeletal muscle and that of young/aged heterogenous muscle-derived human primary cells (HDMCs) over several time points of differentiation (0, 72 h, 7, 10 days). Aged muscle tissue was hypermethylated compared with young tissue, enriched for; pathways-in-cancer (including; focal adhesion, MAPK signaling, PI3K-Akt-mTOR signaling, p53 signaling, Jak-STAT signaling, TGF-beta and notch signaling), rap1-signaling, axon-guidance and hippo-signalling. Aged cells also demonstrated a hypermethylated profile in pathways; axon-guidance, adherens-junction and calcium-signaling, particularly at later timepoints of myotube formation, corresponding with reduced morphological differentiation and reductions in MyoD/Myogenin gene expression compared with young cells. While young cells showed little alterations in DNA methylation during differentiation, aged cells demonstrated extensive and significantly altered DNA methylation, particularly at 7 days of differentiation and most notably in focal adhesion and PI3K-AKT signalling pathways. While the methylomes were vastly different between muscle tissue and HDMCs, we identified a small number of CpG sites showing a hypermethylated state with age, in both muscle tissue and cells on genes KIF15, DYRK2, FHL2, MRPS33, ABCA17P. Most notably, differential methylation analysis of chromosomal regions identified three locations containing enrichment of 6-8 CpGs in the HOX family of genes altered with age. With HOXD10, HOXD9, HOXD8, HOXA3, HOXC9, HOXB1, HOXB3, HOXC-AS2 and HOXC10 all hypermethylated in aged tissue. In aged cells the same HOX genes (and additionally HOXC-AS3) displayed the most variable methylation at 7 days of differentiation versus young cells, with HOXD8, HOXC9, HOXB1 and HOXC-AS3 hypermethylated and HOXC10 and HOXC-AS2 hypomethylated. We also determined that there was an inverse relationship between DNA methylation and gene expression for HOXB1, HOXA3 and HOXC-AS3. Finally, increased physical activity in young adults was associated with oppositely regulating HOXB1 and HOXA3 methylation compared with age. Overall, we demonstrate that a considerable number of HOX genes are differentially epigenetically regulated in aged human skeletal muscle and HDMCs and increased physical activity may help prevent age-related epigenetic changes in these HOX genes.

[Long-term results of surgical and conservative treatment of patients with occlusive-stenotic lesions of carotid arteries]. / Otdalennye rezul'taty khirurgicheskogo i konservativnogo lecheniia patsientov s okkliuzionno-stenoticheskimi porazheniiami sonnykh arterii.

OBJECTIVE: To compare long-term outcomes in patients after carotid endarterectomy and those who refused surgical correction and received only conservative treatment. MATERIAL AND METHODS: There were 1035 carotid endarterectomies performed at the Kemerovo Regional Clinical Hospital and Kemerovo Regional Clinical Cardiology Dispensary for the period 2014-2017. Surgery was refused by 136 patients for the same time. Thus, two groups of patients were formed: 1 - carotid endarterectomy group; 2 - conservative treatment group. INCLUSION CRITERIA: significant carotid stenosis, absence of severe neurological deficit (over 25 scores by the National Institutes of Health Stroke Scale), absence of concomitant diseases limiting long-term follow-up. RESULTS: Lethal outcome (p=0.0038) and fatal acute cerebrovascular accident (p=0.0005) were significantly more common in the 2nd group in long-term follow-up period. Thus, combined endpoint took the greatest values in patients who refused surgery compared with patients who received surgical treatment (p=0.0001). It should be noted that ischemic stroke de novo occurred in 9 (6.6%) patients of the 2nd group after 10.8 ± 2.5 months. This complication required subsequent hospitalization for carotid endarterectomy. CONCLUSION: Preventive role of carotid endarterectomy was convincingly proved in comparison with drug therapy regarding mortality and fatal ischemic stroke in patients with significant carotid stenoses within 2.5 years of follow-up period.

Parkinson's Disease-Associated Changes in the Expression of Neurotrophic Factors and their Receptors upon Neuronal Differentiation of Human Induced Pluripotent Stem Cells.

Parkinson's disease (PD) is a neurodegenerative pathology resulting from the degeneration of dopaminergic (DA) neurons in the substantia nigra (SN). Neurotrophic factors (NTFs) and their receptors are key regulators of the survival, differentiation, and development of neurons. However, the role of these factors in the pathogenesis of PD is still unclear. Here, we analyzed the expression of NTFs and their receptors in human induced pluripotent stem cells (iPSCs) derived from the fibroblasts of patients with PD and healthy donors (HDs). Four PD-derived iPSC lines with different mutations and three cell lines from HDs at different stages of neuronal differentiation were used for RT-qPCR analysis and ELISA. We found that the mRNA levels of most analyzed genes were altered in PD-derived cells compared with those in HD-derived cells at all stages. Importantly, irrespective of PD-associated mutations, the mRNA levels of the BDNF and GDNF genes were mostly increased or unchanged in predominantly DA terminally differentiated neurons (TDNs) compared with those in HD-derived cells. Strikingly, in contrast to BDNF and GDNF mRNA levels, BDNF and GDNF protein levels were lower in almost all PD-derived TDNs than in HD-derived cells, thus indicating the dysregulation of NTF expression at the post-transcriptional level. We suggest that this dysregulation is one of the important signs of PD development.

LogLoss-BERAF: An ensemble-based machine learning model for constructing highly accurate diagnostic sets of methylation sites accounting for heterogeneity in prostate cancer.

Although modern methods of whole genome DNA methylation analysis have a wide range of applications, they are not suitable for clinical diagnostics due to their high cost and complexity and due to the large amount of sample DNA required for the analysis. Therefore, it is crucial to be able to identify a relatively small number of methylation sites that provide high precision and sensitivity for the diagnosis of pathological states. We propose an algorithm for constructing limited subsamples from high-dimensional data to form diagnostic panels. We have developed a tool that utilizes different methods of selection to find an optimal, minimum necessary combination of factors using cross-entropy loss metrics (LogLoss) to identify a subset of methylation sites. We show that the algorithm can work effectively with different genome methylation patterns using ensemble-based machine learning methods. Algorithm efficiency, precision and robustness were evaluated using five genome-wide DNA methylation datasets (totaling 626 samples), and each dataset was classified into tumor and non-tumor samples. The algorithm produced an AUC of 0.97 (95% CI: 0.94-0.99, 9 sites) for prostate adenocarcinoma and an AUC of 1.0 (from 2 to 6 sites) for urothelial bladder carcinoma, two types of kidney carcinoma and colorectal carcinoma. For prostate adenocarcinoma we showed that identified differential variability methylation patterns distinguish cluster of samples with higher recurrence rate (hazard ratio for recurrence = 0.48, 95% CI: 0.05-0.92; log-rank test, p-value < 0.03). We also identified several clusters of correlated interchangeable methylation sites that can be used for the elaboration of biological interpretation of the resulting models and for further selection of the sites most suitable for designing diagnostic panels. LogLoss-BERAF is implemented as a standalone python code and open-source code is freely available from https://github.com/bioinformatics-IBCH/logloss-beraf along with the models described in this article.

[Targeted gene sequencing panels: applicability for neoantigen profiling of colon and rectal adenocarcinoma]. / Vozmozhnosti primeneniia targetnykh panelei dlia opredeleniia neoantigennogo profilia obraztsov adenokartsinomy tolstoi i priamoi kishki.

Cancer immunotherapy represents a promising and rapidly developing approach for the treatment of oncological diseases. Among the methods of personalized adjuvant immunotherapy, neoantigenic peptide-based drugs have demonstrated substantial efficiency. These drugs are designed to target mutant proteins arising from somatic alterations in the genome of tumor cells and thus stimulate immune response against tumor tissues. The methods of individual screening for potentially immunogenic mutations are mostly based on next-generation exome sequencing of tumor samples, which is a complex and costly procedure for clinical application. Targeted gene sequencing panels limited to a certain set of genes represent a reasonable alternative to WES. Targeted sequencing is also more efficient when there is a low amount of the sample DNA available. We have estimated the potential efficiency of targeted oncological panels in terms of somatic neoantigen profiling in colorectal cancer (colon and rectal adenocarcinoma). The clinical practice of identification of frequent somatic variants does not provide enough data for designing an efficient personalized drug when applied to low and medium mutated cancers such as colorectal cancer. Our analysis of 11 commercially available panels containing different number of genes has shown that neither the larger size of a panel nor its initial customization for colorectal cancer provides a significantly better estimation of an individual somatic mutation profile. The optimal approach is to use the general-purpose medium-sized cancer panels (2300-11200 amplicons and/or 150-600 genes). These panels allow to detect a sufficient number of immunogenic epitopes (>3) per patient for over 30-50% of patients.

[GSTP1, APC and RASSF1 gene methylation in prostate cancer samples: comparative analysis of MS-HRM method and Infinium HumanMethylation450 BeadChip beadchiparray diagnostic value]. / Status metilirovaniia genov GSTP1, APC i RASSF1 v obraztsakh raka predstatel'noi zhelezy cheloveka: sravnitel'nyi analiz diagnosticheskoi informativnosti metodov MS-HRM i gibridizatsii na DNK-chipakh illumina Infinium HumanMethylation450 BeadChip.

There is a clear need in molecular markers for prostate cancer (PC) risk stratification. Alteration of DNA methylation is one of processes that occur during ÐÑ progression. Methylation-sensitive PCR with high resolution melting curve analysis (MS-HRM) can be used for gene methylation analysis in routine laboratory practice. This method requires very small amounts of DNA for analysis. Numerous results have been accumulated on DNA methylation in PC samples analyzed by the Infinium HumanMethylation450 BeadChip (HM450). However, the consistency of MS-HRM results with chip hybridization results has not been examined yet. The aim of this study was to assess the consistency of results of GSTP1, APC and RASSF1 gene methylation analysis in ÐÑ biopsy samples obtained by MS-HRM and chip hybridization. The methylation levels of each gene determined by MS-HRM were statistically different in the group of PC tissue samples and the samples without signs of tumor growth. Chip hybridization data analysis confirmed the results obtained with the MS-HRM. Differences in methylation levels between tumor tissue and histologically intact tissue of each sample determined by MS-HRM and chip hybridization, were consistent with each other. Thus, we showed that the assessment of GSTP1, APC and RASSF1 gene methylation analysis using MS-HRM is suitable for the design of laboratory assays that will differentiate the PC tissue from the tissue without signs of tumor growth.

[Genome-wide analysis of DNA methylation in prostate cancer using the technology of Infinium HumanMethylation450 BeadChip (HM450)].

Using the technology of DNA chips Infinium HumanMethylation 450 BeadChip it was analyzed quantitative DNA methylation status in 12 paired samples of prostate adenocarcinoma, and morphologically altered tissues. Analysis of differentially methylated regions of the genome showed an association with abnormal status for 21610 and 3852 hypomethylated hyper-methylated CpG sites. Dominance in the cancer genome hypermethylated sites and their predominant localization in the regulatory regions of genes indicate their possible role in the implementation of mechanisms of gene suppression in the pathogenesis of prostate cancer (PCa). For 14 genes studied were characterized array maximum values hypermethylation in promoter region (> 50% CpG sites) in combination with a high level of methylation differences between treatment groups (> 40%). Role of hypermethylation in some of them: AOX1, KLF8, ZNF154, TMEM106A in the pathogenesis of prostate cancer has been showed previously. Hypermethylation of genes ACSS3, TAC1, TUBA4B, ZSCAN12 not previously been shown for prostate cancer, but is characterized by the association with other cancers. In turn, the differences in the levels of methylation in genes GPRASP1, NKX2-6, ARX, CYBA, EPSTI1, RHCG been documented as a result of a number of genome-research oncology, but has not been studied in detail. To assess the diagnostic potential of epigenetic markers of prostate cancer there was carried out unbiased selection of individual CpG sites most reliably discriminate against tumor samples from a group of no tumor samples. In selected diagnostic model based on logistic regression included 9 CpG sites. Validation of the model was carried out on an independent dataset of methylation of 40 paired samples from the prostate cancer project Atlas of Cancer Genome (TCGA) analyzed on the same version of the DNA chip. Summarized rates of diagnostic informativeness of a model (specificity 95%, sensitivity of 97%, the area under the curve of the diagnostic test (ROC) - 0,96), obtained after validation, allow us to consider these CpG Sites as potential markers for molecular diagnosis of prostate cancer.