β-(1→2)-Glucans constitute a relatively rare and substantially underexplored class of polysaccharides. Of particular interest is the macrocyclic β-(1→2)-glucan from Brucella (CβG), which regarded as a promising diagnostic marker of brucellosis. However, the development of CβG-based diagnostic system requires careful consideration of potential interference from short β-(1→2)-linked gluco-oligosaccharides present in various bacterial commensals and pathogens. To address this challenge, we performed the stereoselective synthesis of a representative series of trisaccharide antigens bearing di-β-(1→2)-glucoside motifs. Several strategies for β-selective insertion of the di-β-(1→2)-glucoside block were evaluated, including approaches employing picolylated and silylated donors as well as donors lacking stereodirecting groups at C-2. Optimal results were achieved using nonparticipating thioglycoside donors activated by a FeCl 3 /TCCA promoter system in acetonitrile. The method proved to be widely applicable to a range of monosaccharide acceptors, affording the target trisaccharides with excellent β-selectivity. The applicability of prepared oligosaccharides for profiling carbohydrate specificity of antibodies was demonstrated by large-scale screening of human donor sera.

Generally, cancer is responsible for nearly every sixth death worldwide. Early cancer revelation can provide successful and low-cost treatment of cancer, enhancing survival rates of cancer patients. This explains the key importance of development of novel highly sensitive systems for revelation of cancers in humans. Ribonucleic acids (RNAs) of several different types (microRNAs, circular RNAs, and small nucleolar RNAs) represent promising cancer biomarkers. At the same time, nanoribbon biosensors allow one to detect cancer-associated RNAs at ultra-low concentrations. Here we focus at experimental results on the detection of cancer-associated RNAs in human plasma with our nanoribbon biosensor, demonstrating promising capabilities of this nanotechnology-based device as a base of highly efficient diagnostic screening platform for early diagnosis of cancers in humans.

The objective of the present study was to assess serum and cancerous tissue biometal levels in colorectal cancer (CRC) patients, and its relation to disease severity. A total of 90 CRC patients and 97 controls were involved in the present study. The level of biometals in blood serum and colon tissues (only in CRC cases) was evaluated by inductively-coupled plasma mass-spectrometry. CRC patients are characterized by lower serum Ca, Fe, Se, and Zn, as well as higher serum Co, Cu, Mg, V, and Cu/Zn ratio compared to healthy controls. The lowest serum Zn levels and the highest Cu concentration and Cu/Zn ratio were observed in patients with the largest tumor size. Regression analysis demonstrated that tumor size is a significant negative predictor of serum Se levels, being positively associated with serum Cu/Zn values. The degree of metastasis to regional lymph nodes was inversely associated with circulating Ca, Co, Mg, Zn, and Mn levels. Serum Mg and Mn levels were positively associated with the stage of the disease and tumor location, respectively. Cancerous tissue Ca and Mo levels were lower, while Mg content was higher compared to healthy adjacent tissues. In cancerous tissues a constant but non-significant trend to elevation of tissue Zn content with increasing tumor size was observed. In addition, serum Cu, Zn, and Cu/Zn values positively correlated with the respective tumor values. These findings demonstrate that altered biometal metabolism is associated with CRC, while systemic Cu/Zn ratio may be indicative of Cu and Zn imbalance in cancerous tissue.

Background/Objectives: Immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have revolutionized cancer immunotherapy, however the clinical relevance of their soluble forms (sPD-1 and sPD-L1) remains less studied. Soluble PD-1 and PD-L1 have been implicated in tumor progression, prognosis, and treatment response across various malignancies. This study aims to provide a comprehensive analysis of sPD-1 and sPD-L1 levels in serum across diverse tumor types, including rare malignancies, and to evaluate their associations with clinicopathological characteristics and prognostic significance. Methods: In this study we analyzed sPD-1 and sPD-L1 levels in serum samples from 675 cancer patients representing a range of malignancies, including ovarian cancer, breast cancer, gastric cancer, colorectal cancer, renal cell carcinoma, and bone tumors. sPD-1 and sPD-L1 concentrations were measured using ELISA. Statistical analyses were performed to evaluate associations between soluble marker concentrations and clinicopathological factors, including tumor stage, size, histological subtype, and survival outcomes. Results: Elevated sPD-L1 levels were observed in several tumor types, including ovarian cancer, renal cell carcinoma, and gastric cancer, where they were associated with features of advanced disease, such as tumor size, stage, and metastases. In contrast, sPD-1 levels showed limited associations, with significant findings solely in gastric cancer and bone tumors, where levels correlated with histological subtype and differentiation. Prognostic analyses identified sPD-L1 as a marker of poor survival outcomes in ovarian cancer and bone tumors, while sPD-1 displayed no consistent prognostic significance. Conclusions: This study identifies the potential of sPD-L1 as a biomarker for tumor progression and prognosis across multiple malignancies. In contrast, sPD-1 showed limited clinical relevance, suggesting the importance of further investigation. These findings contribute to our understanding of soluble immune checkpoint proteins and their integration into personalized oncology strategies.

The expression of long non-coding RNAs (lncRNAs) PSMB8-AS1 and IGFL2-AS1, as well as associated microRNAs miR-802 and miR-382-3p, was analyzed in 42 paired samples of non-small cell lung cancer (NSCLC) with subsequent evaluation of their diagnostic and prognostic significance. The expression of PSMB8-AS1 was reduced in tumor tissue compared to normal lung tissue, while the expression levels of IGFL2-AS1, miR-802, and miR-382-3p were increased. The analysis of the clinical significance of the studied molecules showed that the expression of PSMB8-AS1 correlated with the histological type and localization of the tumor (r = -0.532, p = 0.0003, and r = -0.475, p = 0.003, respectively). ROC analysis for PSMB8-AS1 in the group of patients with squamous cell carcinoma showed that the area under the ROC curve was 0.904 (p < 0.0001), indicating good quality of the diagnostic model and allows us to use the data obtained to further verify it. The analysis of the prognostic significance has shown that the studied non-coding RNAs in general are not prognostic factors for NSCLC. Additional subgroup analysis showed that PSMB8-AS1 is an unfavorable prognostic factor for squamous cell lung cancer (hazard ratio (HR)= 4.482, p = 0.027). Further investigation of non-coding RNAs in NSCLC is promising for identifying new markers for the diagnosis and prognosis of this disease.

Background: Ovarian cancer is one of the most aggressive gynecological malignancies with a high mortality rate related to delayed diagnosis and high rates of resistance to conventional therapies. Results of clinical trials indicate that soluble galectin-3 could be considered as a potentially significant biomarker for malignant neoplasms of various locations. Its increased serum levels are frequently associated with aggressive tumors, risk of metastasis, resistance to therapy, and poor prognosis. However, data on its role and diagnostic value in ovarian cancer remains limited and contradictory. Aim: To analyze the diagnostic and prognostic value of the soluble galectin-3 in patients with various ovarian neoplasms. Methods: This retrospective study included 176 patients with ovarian tumors and 20 healthy donors who were examined and treated from January 2017 to December 2024 at the N. N. Blokhin National Medical Research Center of Oncology and Khabarovsk Territory Regional Clinical Center of Oncology. In all patients, the diagnosis was confirmed by morphological examination of the tumor according to the 2020 World Health Organization (WHO) Classification of Female Genital Tumors. Serum levels of soluble galectin-3 were measured in samples obtained before the initiation of specific treatment with the Human Galectin-3 Quantikine ELISA enzyme immunoassay kit (RD Systems, USA) in accordance with the manufacturer's instructions. Measurements were performed on a BEP 2000 Advance automated enzyme immunoassay analyzer (Siemens Healthcare Diagnostics, Germany) according to the manufacturer’s specifications. Results: One hundred and sixteen patients (116/176) had epithelial ovarian cancer (EOC), 6/176 had non-epithelial ovarian cancer (NEOC), 32/176 were diagnosed with benign ovarian tumors (BOT), and 22/176 with borderline ovarian tumors (BLOT). In the healthy controls, the median galectin-3 level was 8.02 ng/mL being significantly lower than that in the patients with EOC (10.35 ng/mL) (p = 0.0219). In the BOT group, the median galectin-3 level was 7.43 ng/mL, in the BLOT group 7.22 ng/mL, and in the NEOC group 5.49 ng/mL (p 0,999 for all comparisons to the control group). The ROC analysis demonstrated a moderate diagnostic significance of galectin-3 for EOC, with the area under the curve (AUC) of 0.702 and 95% confidence interval (CI) of 0.585 to 0.818 (p = 0.004). With a threshold value of galectin-3 concentration of 8.84 ng/mL, the test sensitivity was 62.93% and specificity 65%. If the median value were used as a cutoff, the sensitivity decreased to 50%, while the specificity increased to 75%. In the EOC group the galectin-3 levels were significantly associated with the patients age, in those above 57 of age its median value was 11.69 ng/mL, being significantly higher compared to the patients ≤ 57 years of age (9.03 ng/mL, p = 0.009). No associations were found between galectin-3 levels and other clinical and morphological characteristics, such as tumor size, disease stage, cancer spreading / metastasis). Depending on the histological type of epithelial tumors, median galectin-3 levels ranged from 9.64 ng/mL (serous type) to 13.18 ng/ml (clear cell type), but the differences were not significant (p = 0.358). In the univariate and multivariate analysis, elevated galectin-3 levels were significant predictors of unfavorable outcome (hazard ratio [HR]: 2.246, p = 0.046 and HR: 1.137, p = 0.017, respectively). Conclusion: Elevated soluble galectin-3 levels is a predictor of unfavorable prognosis in EOC. High serum concentration of this protein may be a promising additional diagnostic marker for EOC.

Background: Dedifferentiated chondrosarcoma (DDCS) is a rare and extremely aggressive variant of mesenchymal bone tumors, with a biphasic structure represented by the classical chondrosarcoma elements, usually of low or intermediate grade, combined with a sharp transition to a highly malignant (high grade) non-cartilaginous sarcoma. The DDCS is associated with a poor outcome, low effectiveness of medical therapy and high mortality rates. One of promising areas of treatment for these tumors is immunotherapy, which requires a more profound understanding of the immunological status of the tumor and composition of its microenvironment. Aim: To analyze the expression of PD-L1, CD4, CD8, CD20 and PU.1 markers in the inflammatory infiltrate of the tumor stroma in the samples of primary DDCS to search for new treatment and prognostic targets, as well as potential predictors of treatment efficacy. Methods: We retrospectively analyzed the results of the immunohistochemical (IHC) studies of the tumor samples obtained from 42 patients with DDCS (18 men and 24 women aged 24 to 94 years; median age 65 years). The study samples of DDCS demonstrated two components, namely, well-differentiated chondrosarcoma and poorly differentiated non-cartilaginous sarcoma represented by pleomorphic undifferentiated sarcoma (n = 33), osteosarcoma (n = 6), rhabdomyosarcoma (n = 2) and angiosarcoma (n = 1). The IHC analysis was performed in the automated mode with a Ventana Bench Mark ULTRA IHC stainer (Ventana Medical Systems, USA) using an optimized protocol and anti-PD-L1 antibodies (clone SP142) and in the manual mode for staining with anti-PU.1, CD4, CD8 and CD20 antibodies. The PD-L1 expression was assessed separately in the dedifferentiated and chondroid components of the tumor. Samples containing PD-L1 expressing lymphocytes were counted separately. Results: PD-L1 was expressed in the dedifferentiated component of 40% of the cases (17/42), in the chondroid component of 26% of the cases (11/42), and in both components in 17% of the cases (7/42). There was no association between PD-L1 expression in different tumor components and clinical and morphological characteristics of the disease. Median survival of the PD-L1 non-expressing patients was 68.6 months, while of those with the expression 7.7 months (p = 0.096). The mean macrophage count in the dedifferentiated tumor component was 17.3 ± 12.8%, that of CD4+ T-cells 4 ± 3.5%, CD8+ T-cells 4 ± 2.4%, and B cells 6.7 ± 3.8%. The analysis of an association between immune cell counts and clinical and morphological characteristics showed that higher tumor infiltration with B-cells was typical for an earlier stage of the disease (p = 0.045). The stromal markers studied did not have any prognostic significance, however there was a trend towards an unfavorable course of the disease (p = 0.112) for those with high macrophagal infiltration of the DDCS samples. The PU.1+ cell counts in the tumor stroma positively correlated with PD-L1 expression both in the chondroid (r = 0.357, p = 0.028) and in the dedifferentiated tumor components (r = 0.343, p = 0.033), as well as with the T cell numbers (r = 0.365, p = 0.026). Conclusion: The results of our IHC studies on the expression of PD-L1, CD4, CD8, CD20, and PU.1 indicate the clinical and prognostic significance of the immune microenvironment of DDCS, opening additional prospects for predicting of the disease outcomes and development of immune therapies. Nevertheless, a more precise delineation of the clinical value of the identified markers requires that studies on larger patient samples should be continued.

Integration of various types of omics data is an important trend in contemporary molecular oncology. In this regard, high-throughput analysis of trace and essential elements in cancer biosamples is an emerging field that has not yet been sufficiently addressed. For the first time, we simultaneously obtained gene expression profiles (RNA sequencing) and essential and trace element profiles (inductively coupled plasma mass spectrometry) for a set of human cancer samples. The biosamples were formalin-fixed, paraffin-embedded primary tumor tissue blocks: 67 for colorectal cancer patients and 18 for other solid cancer types (16 types). Mass spectrometry profiles were obtained for 45 chemical elements: Ag, Al, As, Au, B, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, Ga, Ge, Hg, I, K, La, Li, Mg, Mn, Mo, Na, Ni, P, Pb, Pd, Pt, Rb, Sb, Sc, Se, Si, Sn, Sr, Te, Ti, Tl, Zn, U, V, W, and Zr. The expression levels were profiled for 36,596 known human genes, and the activation levels were assessed for 10,520 human intracellular molecular pathways. For the concentrations of essential elements Ca, Cu, Fe, K, Mg, Na, P, and Zn we detected statistically significant correlations on both gene expression and pathway activation levels for both colorectal cancer samples and at the pan-cancer level. In total, 222/137, 122/220, 1/0, 239/186, 71/44, 1/0, 354/294, 69/82 gene/pathway biomarkers were detected for Ca, Cu, Fe, K, Mg, Na, P, and Zn, respectively. We believe that this first-in-class database provided here will be valuable for multiomics cancer research.

Background: Cadherins are calcium-dependent transmembrane glycoproteins whose extracellular domains mediate homophilic intercellular interactions. Their soluble forms (s-cadherins), generated through proteolytic cleavage of transmembrane proteins or alternative mRNA splicing, are not anchored in the cell membrane and circulate in the extracellular space or peripheral blood. In the context of carcinogenesis, the role of P-cadherin remains a matter of debate: some studies associate P-cadherin with tumor growth suppression, while others indicate its tumor-promoting properties. Publications on the significance of the soluble P-cadherin in various disorders are scarce. Aim: To perform a comparative analysis of serum sP-cadherin levels in healthy women and in patients with malignant and benign ovarian tumors to assess the clinical significance of the marker. Methods: The retrospective study included 56 patients with epithelial malignant ovarian tumors (median age 57 years), 10 patients with benign ovarian tumors (median age 55 years), and 11 healthy women (median age 56 years) who underwent examination and treatment from 2023 to 2024 in three oncology clinics. Serum levels of sP-cadherin before the initiation of specific treatment were determined with the Human P-Cadherin ELISA Kit (RayBiotech, USA). Results: In the ovarian cancer group, the majority of the patients had the serous type of the tumor (n = 46, 82%), stage III to IV of the disease (n = 45, 80%), T3 and T4 tumors (n = 42, 75%), mostly without regional (N0: n = 41, 73%) and distant metastases (M0: n = 43, 77%). The results of the ROC analysis showed that serum levels of the soluble P-cadherin could not be used as a reliable diagnostic criterion for ovarian malignancies: the area under the curve (AUC) was 0.793 (confidence interval 0.671 to 0.915; p = 0.002). At the optimal cut-off value of 3.01 ng/mL, the test’s sensitivity and specificity were 77% and 73%, respectively. The serum sP-cadherin levels did not show a significant correlation with the key clinical and morphological characteristics of ovarian cancer. Conclusion: Patients with ovarian cancer have an increased serum sP-cadherin level. Further research on this glycoprotein to assess its role in disease outcomes and chemotherapy efficacy is expedient.

Background: Renal cell carcinoma (RCC) is a highly immunogenic neoplasm and a promising target for the development of new approaches to immunotherapy. Galectins can modulate immune response, actively participating in inflammation, and help the tumor cells to escape host immune reaction. Some members of the galectin family could further become promising diagnostic or prognostic markers of various malignancies. However the data obtained are not unambiguous, and in some observations are extremely contradictory. We have demonstrated previously a significant increase of soluble galectins-1, -3 and -9 levels in serum of RCC patients before the initiation of anti-tumor therapy. Aim: To analyze an association between serum galectins-1, -3, -4, -7, -9 levels and overall survival of RCC patients with various stages of the tumor process. Methods: We retrospectively analyzed the impact of baseline soluble galectins-1, -3, -4, -7, -9 levels on overall survival of 129 patients with primary RCC who had undergone examination and treatment at the N. N. Blokhin National Medical Research Center of Oncology from 2019 to 2023. Surgery had been performed in all patients, and 10 of them had systemic target treatment or immunotherapy after surgery. Serum galectins concentrations were measured before the start of specific treatment with standard enzyme immunoassay kits. Results: The patients (n = 129) were followed up for 0.3 to 64.6 months (median, 39.3 months) after surgery. During this follow-up 32 (24.8%) patients died. They survived from 0,3 to 50.8 months (median, 20.2 months) after the initiation treatment. The patient groups selected depending on the corresponding marker levels (above or below the median) were not different in their clinical and pathologic characteristics and the treatment performed. Only pre-treatment serum galectin-3 and galectin-9 levels were associated with overall survival rates. Serum concentrations of galectin-3 and galectin-9 above the median level (10.1 ng/mL and 9.2 ng/mL) significantly decreased the 5-years overall survival of RCC patients by 21.1% and 17.6% respectively. Conclusion: Measurement of serum galectin-3 and galectin-9 concentrations can be used as supplementary criteria for the assessment of overall survival prognosis in patients with RCC.

Background: Galectin-4 is a member of β-galactoside-binding protein family, which is mainly expressed in gastrointestinal epithelial cells and also secreted into the extracellular environment. Studies have shown that galectin-4 is involved in the regulation of proliferation and metastasis of gastric and pancreatic cancer tumor cells. The results of studies on the clinical significance of galectin-4 in colorectal cancer (CRC) are ambiguous: some studies showed its increased expression, associated with aggressive course and unfavorable prognosis, while others showed its decrease. Aim: To analyze the clinical significance of the soluble form of galectin-4 in CRC. Methods: We retrospectively analyzed the medical records of 130 patients (mean age, 61 year) with a verified diagnosis of CRC, who had been examined and treated from 2016 to 2022. Galectin-4 levels were measured in serum obtained by a standard method before the start of specific treatment, by the enzyme-linked immunosorbent assay (ELISA). The control group consisted of 30 healthy donors (mean age, 53 years). Results: The median concentration of galectin-4 in the CRC patients was higher than in the control group (531.9 [350.6–1380] pg/mL vs. 330.1 [173.0–566.4] pg/mL, p = 0.0004). The ROC analysis demonstrated maximum sensitivity and specificity of the test (66% and 67%, respectively) at a threshold value of 426.3 pg/mL (area under the curve 0.706 with 95% confidence interval 0.594–0.817; p = 0.0005). The galectin-4 levels were higher at advanced stages of the disease (p = 0.002) and in the presence of distant metastases (p 0.0001). Cox regression analysis showed that tumor size and distant metastases were independent prognostic factors (hazard ratio (HR) = 3.87; p = 0.0439; HR = 720.4; p = 0.0062, respectively) associated with decreased survival. Galectin-4 is not a prognostic marker of CRC (HR = 2.434; p = 0.079). Conclusion: The amounts of the soluble galectin-4 are associated with tumor progression, indicating a possible tumor-promoting function of this protein. However, its diagnostic value remains limited, as the method of serum galectin-4 determination has shown insufficient sensitivity and specificity for its routine use for the diagnosis of CRC. According to the results of univariate and multivariate analyses, serum galectin-4 is not a significant prognostic marker of CRC.

Introduction. Primary bone sarcomas are relatively rare neoplasms. They occur predominantly in adolescents and young adults, are characterized by an aggressive clinical course and a high metastatic potential, have a poor prognosis. In this regard, the problem of stratifying the risk of metastasis and death in order to select the optimal treatment tactics always remains relevant. The study of such markers as endostatin, vascular endothelial growth factor (VEGF), insulin-like growth factors IGF-1, IGF-2 as potentially informative predictors of survival in patients with bone sarcomas is pathogenetically determined by their involvement in the processes of tumor growth and metastasis. Aim – to analyze the relationship between pre-treatment serum levels of endostatin, VEGF, IGF-1 and IGF-2 with overall survival rates in patients with bone sarcomas. Material and methods. An analysis of overall survival rates was carried out in 134 patients with malignant bone tumors aged from 1 to 73 years (Me=27.0 years; Q1–Q3: 18.0 – 43.0 years), among them 87 men (64.9%) and 47 women (35.1%). All patients comprised 4 groups: osteosarcoma (n=58), undifferentiated pleomorphic sarcoma (n=5), Ewing sarcoma (n=29), chondrosarcoma (n=42). In all of them, before the start of specific antitumor treatment, the levels of endostatin, VEGF, IGF-1, and IGF-2 in the blood serum were determined using enzyme immunoassay. The follow-up period ranged from 1 to 229 months (Me=23.0 months; Q1–Q3: 10.0–121.0 months). To analyze overall survival, life tables and Kaplan–Meier curves were constructed. The effect of the studied serum markers on survival rates was assessed using the logrank test and Cox proportional hazards regression model. Results. During observation, death occurred in 51 patients (38.1%). In the group of deceased patients, serum levels of endostatin and IGF-2 were statistically significantly increased compared to the group of surviving patients (p 0.001 and p=0.011, respectively). Kaplan-Meier survival analysis using the logrank test revealed statistically significant differences in overall survival between the four groups of patients with different serum levels of endostatin, IGF-1 and IGF-2. The Cox regression method established the prognostic significance of endostatin as a predictor of overall survival (HR=1.012; p=0.013). Conclusion. Endostatin, IGF-1, IGF-2 can serve as predictors of overall survival of patients with bone sarcomas.

Background: Galectins are a family of β-galactoside binding proteins that regulate the vast majority of cellular functions, including proliferation, migration, adhesion, and phagocytosis in both health and disease. More and more experimental and clinical evidence indicates that galectins are involved in many stages of carcinogenesis, including patients with renal cell carcinoma (RCC). Aim: To analyze the clinical significance of soluble forms of galectins -1, -3, -4, -7, -9 in patients with various histological RCC types. Materials and methods: We performed a retrospective analysis of the clinical significance of galectins -1, -3, -4, -7, -9 in the serum of 140 RCC patients (84 with clear cell RCC (ccRCC), 38 with papillary (papRCC), 18 with chromophobe (chrRCC)) and in 73 healthy donors (control group), who were examined and treated from 2019 to 2023 in the N. N. Blokhin National Medical Research Center of Oncology. Galectin levels were measured in serum (obtained according to standard methods before the initiation of specific treatment) with an enzyme-linked immunosorbent assay. Results: There was a significant increase in serum galectin -1, -3, -9 levels in the whole RCC patient group, compared to the healthy donor control group; no increase was found for galectins -4 and -7. Serum galectin-1 levels in the ccRCC and papRCC patients were significantly higher than those in the controls (p = 0.0003 and p = 0.0135, respectively). No association between the serum galectins -1 and -7 and the clinical and morphological characteristics of RCC was found; however, serum galectin-7 levels in the papRCC patients correlated with the grade of tumor differentiation (r = -0.592; p = 0.001). The area under the ROC curve (AUC) for galectin-1 in ccRCC was 0.721 (p 0.0001), in papRCC 0.673 (p = 0.0086), and in chrRCC 0.576 (p = 0.355). For galectin-7, the ROC AUC values were 0.527 (p = 0.634) in ccRCC, 0.513 (p = 0.845) in papRCC, and 0.566 (p = 0.425) in chrRCC. In all histological types of RCC, there was a significant increase in serum galectin-3 compared to the controls (ccRCC, p = 0.0208; papRCC, p = 0.0014; chrRCC, p = 0.0041). The ROC analysis for galectin-3 in patients with RCC of various histological types showed AUC = 0.721 (p 0.0001) for ccRCC, 0.673 (p = 0.0086) for papRCC, and 0.576 (p = 0.355) for chrRCC. Galectin-9 levels was directly and significantly associated with the tumor size, as well as with regional metastases (r = 0.251, p = 0.021; r = 0.239, p = 0.028, respectively). The AUC values for galectin-4 were 0.619 (p = 0.021) in ccRCC, 0.577 (p = 0.214) in papRCC, and 0.534 (p = 0.666) for chrRCC. For galectin-9, they were 0.649 (p = 0.0075), 0.613 (p = 0.087), and 0.539 (p = 0.637), respectively. Conclusion: The study has demonstrated a certain association between serum galectin -1, -3, -4, -7, and -9 in the patients with RCC of various histological types. Although the results of the ROC analysis indicated average quality of the model, which does not allow for the use of the obtained data for diagnostic purposes, it is necessary to continue the research for better understanding of the mechanisms of galectin functioning, before galectin-based therapeutic agents would be introduced into clinical practice for the treatment of RCC.

There are three types of metastases in ovarian cancer: lymphogenous, hematogenous, and peritoneal. Dissemination of the tumor in the peritoneum is directly related with the development of ascites and a poor prognosis. The purpose of this study is to determine changes in the methylation level of a group of long non-coding RNA (lncRNA) genes at different stages of ovarian cancer progression. The methylation level of 7 lncRNA genes (LINC00472, LINC00886, MAFG-DT, SNHG1, SNHG6, TP53TG1, and TUG1) was studied by quantitative methyl-specific PCR in 93 samples of ovarian tumors and 75 paired samples of histologically normal tissue, as well as in 29 peritoneal macroscopic metastases. Using the nonparametric Mann—Whitney test, a significant (p<0.001) increase in the level of methylation of the LINC00886, SNHG1, SNHG6, and TUG1 genes in the tumor tissue was shown. For the LINC00472, LINC00886, and SNHG6 genes, a significant relationship was found with the clinical stage (p≤0.001), as well as with the appearance of metastases for the LINC00472 (p<0.001) and SNHG6 (p=0.005) genes. There was a significant increase in the level of methylation of MAFG-DT and TP53TG1 (p<0.001) genes, as well as a decrease in LINC00886 (p=0.003) in peritoneal metastases relative to the primary focus. Methylation of the LINC00472 and SNHG6 genes can be considered as a factor in initiating ovarian cancer metastasis, and methylation of the LINC00886, MAFG-DT, and TP53TG1 genes as a colonization factor for metastases in the peritoneum. Thus, a relationship between methylation of a group of lncRNA genes at different stages of ovarian cancer dissemination was shown, which is important for understanding the mechanisms of these processes and for developing innovative approaches to ovarian cancer therapy.

The expression of long non-coding RNA (lncRNA) LINC01508 was studied in tumor samples from patients with non-small cell lung cancer (NSCLC), and its clinical significance was evaluated. The expression of LINC01508 lncRNA was measured in 16 pairs of NSCLC samples and its association with clinical and morphological features of the disease and prognosis analyzed. A comparative analysis showed a significant decrease in the expression of LINC01508 in tumor lung tissue in comparison with the surrounding normal lung tissue. The informativity of the diagnostic method was tested using ROC curve analysis and calculation of the area under the curve (AUC) for LINC01508 in NSCLC patients, which showed an AUC of 0.875 (p=0.001). No significant associations of LINC01508 expression level with clinical and morphological characteristics of the disease were found. The analysis of prognostic significance showed that high expression of LINC01508 in NSCLC samples was a favorable prognostic factor. Despite the fact that the results did not reach statistical significance (p=0.107), the median survival rate for patients with low LINC01508 expression was 16 months, while for patients with high expression, it was not reached during the follow-up period. We believe that LINC01508 can be a promising independent prognostic marker for NSCLC.

Cancer is a major global health problem. The type of malignant neoplasm and the potency of the immune response against tumors are two of the key factors influencing the outcome of the disease. The degree of tumor infiltration by lymphocytes plays an important role in antitumor response development, generally correlating with a favorable prognosis of treatment for certain cancers. We analyzed the abundance of tumor-infiltrating B cells (TIBs) in solid tumors of different cancers. TIBs were shown to be more abundant in colon and sigmoid colon cancer samples compared with cecal, rectal, and kidney cancer samples. The median and interquartile range of the TIB fraction were 11.5% and 4-20% in colon cancer, 6% and 3-11% in sigmoid colon cancer, 2.7% and 0.7-3.7% in cecal cancer, 2.5% and 0.9-3.6% in rectal cancer, 1.4% and 1.0-2.3% in kidney cancer, and 3.0% and 1.8-12% in lung cancer, respectively. However, there were no significant differences in the abundance of TIBs among samples at different stages of the cancer. Hence, investigation of the B cell response in colon cancer is of particular interest, since increased quantities of TIBs may indicate the existence of immunogenic tumor markers or the cell-cell interactions involved in disease progression. We believe that studying the diversity of TIBs in colon cancer will increaseour understanding of the mechanisms of the disease, contributing to the identification of new molecular targets for targeted oncotherapy.

Rationale: Long non-coding RNAs (lncRNAs) influence tumor cell properties during the onset and progression of lung malignancies; however, their diagnostic and prognostic significance has not been determined. We have previously shown that when non-small cell lung cancer (NSCLC) cells acquire a more malignant phenotype (under the influence of macrophagal cytotoxic activity) compared to the original cell lines, the expression of several lncRNAs, in particular PSMB8-AS1, MBNL1-AS1, and OLMALINC, is altered compared to the original cell lines. Aim: A comparative analysis of lncRNAs PSMB8-AS1, MBNL1-AS1, and OLMALINC expression in tissue samples from lung tumors and conditionally normal areas of the lungs and an assessment of the lncRNAs clinical significance. Methods: We have analyzed surgical samples of the tumor and conditionally normal tissue from 16 patients with a verified diagnosis of NSCLC. The expression level of lncRNAs PSMB8-AS1, MBNL1-AS1 and OLMALINC was assessed by real-time polymerase chain reaction. To analyze the long-term treatment results and clinical significance of the studied genes, the patients were divided into two comparison groups depending on the relative level of lncRNAs expression (above or below the median). Results: The expression of lncRNAs PSMB8-AS1, MBNL1-AS1 and OLMALINC in the lung tumor tissue was significantly reduced compared to the conditionally normal tissues (p = 0.0034; p = 0.002 and p = 0.0172, respectively). Analysis of the association between the expression of these lncRNAs with clinical and morphological characteristics, such as disease stage, tumor size, presence of regional and distant metastases was unable to identify any regular patterns. The expression of lncRNAs PSMB8-AS1, MBNL1-AS1 and OLMALINC was not a significant prognostic factor (p = 0.364; p = 0.759 and p = 0.184, respectively). However in the case of high OLMALINC and PSMB8-AS1 expression, median survival was 47 months, while in the case of their low expression, median survival was not achieved during the follow-up. The expression of lncRNA PSMB8-AS1 in NSCLC tumors positively correlated with the expression of lncRNA OLMALINC (r = 0.680, p = 0.007), which may indicate their functional interplay or the presence of common regulatory mechanisms. Conclusion: The NSCLC tumors demonstrated aberrant expression of PSMB8-AS1, MBNL1-AS1, and OLMALINC lncRNAs. A more detailed study of their expression in various cell types and their regulatory role would allow for validation of new therapeutic targets in NSCLC, as well as for development of alternative therapies.

Клиническая и прогностическая значимость sPD-1 и sPD-L1 при раке яичников 1 Федеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр онкологии имени Н.Н.Блохина» Министерства

Aim. To conduct a comparative assessment of the content of kisspeptin (KISS1) metastasis suppressor in the blood serum of apparently healthy individuals and patients with lung cancer (LC) and to analyze the associations between the KISS1 level and clinical and pathological characteristics of the disease.Materials and methods. The study included 74 LC patients and 46 apparently healthy individuals. Stage I LC was diagnosed in 8 patients, stage II LC – in 7 patients, stage III LC – in 28 patients, and stage IV LC – in 31 patients. According to the histologic pattern, 32 tumors were characterized as adenocarcinoma, 29 – as squamous-cell carcinoma, 11 – as small-cell LC (SCLC), and 2 – as large-cell lung carcinoma. The pre-treatment KISS1 level in the blood serum was determined using the enzyme-linked immunosorbent assay kit (KISS1, CloudClone Corp., USA).Results. The median serum KISS1 level in LC patients was 213 (range 7.8–716) pg / ml and was significantly higher than in the control group – 83.4 (0–180) pg / ml (p < 0.0001). The ROC analysis of the diagnostic value of serum KISS1 level demonstrated that the sensitivity of the test in relation to the healthy controls was 70% at a cutoff value of 152 pg / ml, and the specificity was 85% (AUC – 0.817; р < 0.0001). In stage I–II LC, the sensitivity did not exceed 50%. The level of KISS1 in the blood serum did not depend on the histologic type of the tumor. No significant differences in the serum KISS1 levels were observed both between non-small cell lung cancer (NSCLC) on the whole and neuroendocrine SCLC and between the main histologic types of NSCLC. The level of KISS1 increased with the disease stage (p < 0.05). However, none of the TNM staging system indices significantly influenced the level of the marker. No differences were found between serum KISS1 levels in patients with central or peripheral localization of the tumor.Conclusion. The KISS1 level was elevated in LC patients compared to healthy controls and was a stage-dependent marker. It has high diagnostic specificity but insufficient sensitivity, especially at early stages of the disease. Based on the results of this study and literature data on the role of KISS1in NSCLC, we conclude that clinical implications of KISS1 in this disease require further research.