Malignant transformation of any cell is associated with numerous physiological and morphological disorders at both genomic and protein levels, a variety of macromolecules being involved in. However, the tumour development and metastasis depends on not only the molecular characteristics of the tumour cell but also its interaction with the surrounding extracellular matrix (ECM), which is an important and necessary part of any tissue. An important role in this process belongs to the complex protein-carbohydrate molecules – proteoglycans (PG), which are one of the main component of ECM and cell surface of any tissue and are tightly involved in cell-cell and cell-matrix interactions and signaling. During carcinogenesis, significant changes in the PG structure and composition occur both at the surface of tumour cells and surrounding ECM, resulting in the transformation of normal ECM into a tumour microenvironment and deterioration of cell-cell and cell-matrix communication. Further, the tumorigenic niche contributes to active proliferation of the cancer cells, tumour development and metastasis. At present, many key PG are identified as possible diagnostic and prognostic molecular markers and target molecules for the creation of new antitumor drugs.

The review describes the main PG types, their structure, localisation, functional role in normal cell and tissue physiology and participation in molecular mechanisms of carcinogenesis.

Epigenetics is a science studying mechanisms of heritable changes in gene function that occur without a change in the DNA sequence. One of the most important marks of epigenetic misbalance of cell genome is an replication asynchrony of genes with biallelic expression. Interphase fluorescence in situ hybridization (I-FISH) in phytohaemagglutinin-stimulated lymphocytes of peripheral blood is a proper method of estimation of aberrant DNA replication time e. g. DNA replication asynchrony. In this review we analyzed reports referring to asynchronous DNA replication of biallelically expressed genes in lymphocytes of peripheral blood of cancer patients. Analysis shows the DNA replication asynchrony is a nonspecific tumor marker observing both in tumor cells and lymphocytes of peripheral blood in oncohematological patients and patients with solid tumors. It’s stated the frequency of lymphocytes with asynchronous DNA replication of studied genes in cancer patients is increased significantly compares with healthy donors and is enhanced during malignance process. It gives the opportunity of potential using asynchronous replication as molecular genetic marker for cancer patients early revealing.

Objective: to evaluate the possibility of using a highly sensitive method of “enriched” polymerase chain reaction followed by DNA melting analysis (PCR-DMA) for target liquid biopsy of cancer patients.

Materials and methods. The “enriched” PCR-DMA was used for mutation scanning of KRAS (codons 12 and 13) in tumor and blood plasma of 20 patients with colorectal cancer.

Results. Activated oncogene was found in tumor tissue of 16 patients and in blood plasma of 5 patients (confirmed by sequencing). Mutant KRAS alleles were also found in tumor and plasma of another 2 patients, but in very low concentrations that did not allow their validation by Sanger sequencing. Thus, in our study the target liquid biopsy was successful in ~35 % patients. Since the plasma tests were carried out after repeated medical procedures causing mass death of tumor cells, the actual efficiency of this approach may appear significantly higher.

Background. It has been proved that for the nasopharyngeal carcinoma (NPC) the etiological agent is the Epstein–Barr virus (EBV). Being an ubiquitous infection, EBV, under certain conditions, is able to display its oncogenic potential. Among a wide range of tumors associated with EBV, the NPC occupies a special place because it is characterized by a geographically and ethnically heterogeneous distribution, suggesting that in the pathogenesis of NPC, in addition to EBV, an important role is played by other factors, such as genetic predisposition to this neoplasm. Among known genetic factors influencing the frequency of NPC development, the human leukocyte antigen (HLA) complex occupies an important place, as it plays a central role in the presentation of viral antigens to the immune system. In Russia, the association of HLA alleles with the risk of EBV associated forms of NPC development and with development of other oral cavity tumors (OOCT), not associated with the virus, has not been studied. In the literature there are contradictory information about HLA genes, which determine the predisposition to the emergence of these tumors, and their role in the initiation and formation an immune response to EBV proteins.

Objective: to study the distribution of the of DQA1-, DQB1-, DRB1-HLA class II gene variants associated with respectively the risk or resistance to the development of NPC and OOCT and with a high and low level of antibody response to EBV main proteins. A group of healthy persons served as a control.

Materials and methods. Blood samples from 62 patients with NPC, 44 patients with OOCT, and as control, 300 healthy individuals, were used in the study. The blood serum samples of NPC and OOCT patients were tested for the presence of immunoglobulin classes G and A antibodies to capsid and early EBV antigens by indirect immunofluorescence. All serum samples of patients and healthy individuals were genotyped on HLA-DQA1, -DQB1 and -DRB1 by the method of multi-primer amplification by sequence-specific primers by real-time polymerase chain reaction.

Results. In NPC patients, an increase in the frequency of HLA-DRB1*08 was found when compared with the frequency of a similar allele in healthy individuals (5.6 % vs 1.8 %; odds ratio (OR) 3.2; 95 % confidence interval (CI) 1.1–9.1; p = 0.02), and, on the contrary, a lower HLA-DQB1*0301 frequency was detected (16.1 % vs 25.3 %; p <0.05) than in healthy individuals. The data obtained suggest that the HLA-DRB1*08 gene is associated with an increased sensitivity to NPC.

In OOCT patients, HLA-DQB1*0502–4 and HLA-DRB1*16 variants were less common than in healthy individuals (1.1 % vs 6.8 %; p <0.05 and 1.1 % vs 6.7 %; OR 0.16; 95 % CI 0.01–1.08; p <0.05, respectively), suggesting that the HLA-DQB1*0301 gene is associated with resistance to NPC, and HLA-DQB1*0502–4 and HLA-DRB1*16 variants – with resistance to OOCT. It is interesting to note the difference in the frequency of HLA-DRB1*13 between NPC and OOCT patients (17.7 % vs 6.8 %; OR 2.9; 95 %

CI 1.1–8.6; p <0.05). One can suggest that this difference is related to the proven involvement of EBV in the NPC development. There were no other differences in the frequencies of class II HLA genes between the groups of NPC and OOCT patients. For the first time in Russia the importance of alleles DQA1, DQB1 and DRB1 of the HLA gene for the NPC and OOCT development, malignant tumors, respectively associated and non-associated with EBV, was studied. The results of the investigation completed together with known literature data allow us to conclude that the above alleles of the HLA class II gene can serve as a factor predisposing to the development of NPC in Russia.

Conclusion. However, in order to establish a strict association between a specific HLA haplotype and the NPC and OOCT incidence, the information obtained is insufficient due to the complexity and variability of the genetic control of immune responses controlling the tumor process. A comprehensive study of this issue using different immune response genes and populations of different ethnic origins will probably help to elucidate the effect of genetic polymorphism on the risk of NPC and OOCT development in Russia.

Background. Most modern studies are limited to the study of only germline mutations of the BRCA1 gene (most often 5382insC). And there are very few works that characterize the different somatic changes in the BRCA1 gene in the tumor, in particular the expression of this gene and its relation to the effect of chemotherapy. Given the linkage of the hereditary BRCA1 mutation with the high efficacy of platinum drugs, it can be assumed that the expression of the BRCA1 gene will be associated with a high sensitivity of the neoplasm to platinum drugs as well.

Objective: study of the relationship of BRCA1 gene expression to the efficacy of neoadjuvant chemotherapy (NAC) in breast tumors.

Materials and methods. Study included 105 patients with breast cancer T1–4N0–3M0 (IIA–IIIB stage). The diagnosis of breast cancer was verified morphologically. The initial expression of BRCA1 was evaluated in the tumor material. RNA was extracted from biopsy specimens of breast tumor tissue. Expression profiling of the BRCA1 gene was carried out using quantitative real-time polymerase chain reaction.

Results. Expression of the BRCA1 gene was evaluated as a result of the study. There was shown its weak correlation with clinico-morphological parameters of patients with breast cancer and parameters of the tumor process. It has been established that an objective response to NAC is associated with a high level of BRCA1 when taxotere is used in monoregime (p = 0.03) and in the CAX (cyclophosphamide, doxorubicin, xeloda) scheme (p = 0.05). Nevertheless, it was shown that, regardless of the regimen used and the number of another NAC courses, high expression of the gene being studied (more than 1.5) in the primary tumor in 70 % of cases generally results in a lack of an objective response to treatment, compared with a low level (less than 0.3) (Fisher test; p = 0.03).

Background. Multiple myeloma (MM) is a hematologic malignancy of plasma cells. The microenvironment plays a key role in MM cell survival and drug resistance through release of soluble factors, expression of adhesion molecules and release of exosomes (EXs). The role that EXs, released by MM cells have in cell-to-cell communication and signaling in the bone marrow is currently unknown. EXs as a source of markers for MM diagnostics are also not studied.

Objective: to use proteomic profiling of EXs as a tool to identify circulating tumor associated markers in MM patients.

Results. The proteome composition of EXs obtained from plasma of patients with MM and multiple sclerosis was studied for the first time. nano-HPLC–MS/MS analysis identified a total of 332 proteins in the EXs of both groups of patients and determined the proximity of their qualitative composition. For the first time, 12 differentially expressed proteins were detected, the levels of which were significantly increased in EXs from patients with MM. This allowed us to consider them as potential markers of the disease.

Conclusion. Proteomic analysis of EXs obtained from plasma of patients with MM is an important method for finding disease markers.