BackgroundCervical screening, aimed at detecting precancerous lesions and preventing cancer, is based on cytology and HPV testing. Both methods have limitations, the main ones being the variable diagnostic sensitivity of cytology and the moderate specificity of HPV testing. Various molecular biomarkers are proposed in recent years to improve cervical cancer management, including a number of mRNAs encoded by human genes involved in carcinogenesis. Many scientific papers have shown that the expression patterns of cellular mRNAs reflect the severity of the lesion, and their analysis in cervical smears may outperform HPV testing in terms of diagnostic specificity. However, such analysis has not yet been implemented in broad clinical practice. Our aim was to devise an assay detecting severe cervical lesions (≥HSIL) via analysis of cellular mRNA expression in cytological smears.MethodsThrough logistic regression analysis of a reverse-transcription quantitative PCR (RT-qPCR) dataset generated from analysis of six mRNAs in 167 cervical smears with various cytological diagnoses, we generated a family of linear classifiers based on paired mRNA concentration ratios. Each classifier outputs a dimensionless decision function (DF) value that increases with lesion severity. Additionally, in the same specimens, the HPV genotyping, viral load assessment, diagnosis of cervicovaginal microbiome imbalance and profiling of some relevant mRNAs and miRNAs were performed by qPCR-based methods.ResultsThe best classifiers were obtained with pairs of mRNAs whose expression changes in opposite directions during lesion progression. With this approach based on a five-mRNA combination (CDKN2A, MAL, TMPRSS4, CRNN, and ECM1), we generated a classifier having ROC AUC 0.935, diagnostic sensitivity 89.7%, and specificity 87.6% for ≥HSIL detection. Based on this classifier, a two-tube RT-qPCR based assay was developed and it confirmed the preliminary characteristics on 120 cervical smears from the test sample. DF values weakly correlated with HPV loads and cervicovaginal microbiome imbalance, thus being independent markers of ≥HSIL risk.ConclusionThus, we propose a high-throughput method for detecting ≥HSIL cervical lesions by RT-qPCR analysis of several cellular mRNAs. The method is suitable for the analysis of cervical cytological smears prepared by a routine method. Further clinical validation is necessary to clarify its clinical potential.

Molecular genetic events are among the numerous factors affecting the clinical course of papillary thyroid carcinoma (PTC). Recent studies have demonstrated that aberrant expression of miRNA, as well as different thyroid-related genes, correlate with the aggressive clinical course of PTC and unfavorable treatment outcomes, which opens up new avenues for using them in the personalization of the treatment strategy for patients with PTC. In the present work, our goal was to assess the applicability of molecular markers in the preoperative diagnosis of aggressive variants of papillary thyroid cancer. The molecular genetic profile (expression levels of 34 different markers and BRAF mutations) was studied for 108 cytology specimens collected by fine-needle aspiration biopsy in patients with PTC having different clinical manifestations. Statistically significant differences with adjustment for multiple comparisons (p < 0.0015) for clinically aggressive variants of PTC were obtained for four markers: miRNA-146b, miRNA-221, fibronectin 1 (FN1), and cyclin-dependent kinase inhibitor 2A (CDKN2A) genes. A weak statistical correlation (0.0015 < p < 0.05) was observed for miRNA-31, -375, -551b, -148b, -125b, mtDNA, CITED1, TPO, HMGA2, CLU, NIS, SERPINA1, TFF3, and TMPRSS4. The recurrence risk of papillary thyroid carcinoma can be preoperatively predicted using miRNA-221, FN1, and CDKN2A genes.

Background:Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) contribute to more than 95% of thyroid malignancies. However, synchronous PTC and FTC are less common; it is most commonly discovered incidentally as synchronous malignancies during operation, which adds difficulties to intraoperative decision-making and postoperative treatment. Therefore, we analyzed the clinicopathological characteristics and prognosis of patients with PTC and FTC in our center.Methods:We conducted a search of single PTC, single FTC, and synchronous PTC/FTC patients who received initial surgery treatment at Fudan University Shanghai Cancer Center from 2006 to 2018 and collected paraffin-embedded samples of synchronous patients. Clinicopathological characteristics were collected from the electronic medical record system. Follow-up was performed through telephone contact or medical records. Exome sequencing was performed by ThyroLead panel.Results:Total of 42 synchronous PTC/FTC patients, 244 single FTC patients, and 2,959 single PTC patients were included. It showed a similarity between the clinicopathological features of synchronous thyroid cancer patients and single PTC patients, with a greater proportion of females, higher probabilities of lymph node metastasis, and higher rate of concurrence of Hashimoto's disease. The disease-free survival (DFS) curve indicated a worse prognosis of the synchronous group and single PTC group compared to the single FTC group, who had a propensity for neck lymph node recurrence; however, logistic multivariate regression analysis did not find any factor related to recurrence in the synchronous group. After re-checking pathology, DNA extraction, and quality control, genetic alteration information of 62 samples including primary tumors and metastatic lymph nodes from 35 synchronous cancer patients was displayed. In total, 81 mutations and 1 fusion gene were identified, including mutations related to outcomes and targeted therapy. Besides, some rare mutations in thyroid cancer were found in these patients.Conclusions:To conclude, synchronous PTC/FTC tend to be incidentally discovered during or after operation, behaving more like single PTC. The prognosis of synchronous patients is worse than that of single FTC patients and supplemental cervical lymph node dissection, total thyroidectomy, and postoperative radioiodine therapy should be taken into consideration after diagnosis. The next-generation sequencing (NGS) showed a unique molecular feature of synchronous patients with some rare mutations.

Objective. The strategy of active surveillance for papillary thyroid microcarcinoma (PTMC) is currently becoming more popular in the global medical community. The pivotal criterion for choosing the active surveillance strategy is the absence of any signs of lymphogenic or distant metastases. In the present work, we assessed the diagnostic accuracy of molecular genetic markers in predicting the metastatic potential in patients with PTMC. Methods. The expression level of 33 molecular genetic markers in cytology samples from 92 patients with PTMC with the known histological diagnosis, including 32 with metastases to regional cervical lymph nodes, was assessed. The list included 22 genes and 11 microRNAs. The presence of the somatic BRAF V600E mutation was investigated separately. Results. In patients with metastatic PTMC, the HMGA2 gene, the TIMP1 gene, and the FN1 gene were more active, and microRNA-146b expression was upregulated. Downregulated expression of microRNA-7 and -148b was also detected in metastatic tumors, which is indicative of their tumor suppressor role. Metastatic tumors were characterized by on average 11-fold lower activity of DIO1, eightfold lower expression of the TFF3 gene, fourfold lower expression of TPO. All the markers, except for BRAF mutation, have high sensitivity (84.5–90.6%) for detecting metastatic PTMC but low specificity (~ 50%). Conclusions. Application of molecular markers for predicting lymphogenic metastatic spread in patients with PTMC can possibly supplement the existing risk grading systems. These studies are relatively simple to conduct and available as early as at the preoperative stage.

Aim . To develop a method for noninvasive diagnosis of external genital endometriosis based on plasma microRNA concentrations. Materials and Methods . 80 women of reproductive age who were admitted to the gynecological department for routine laparoscopy were retrospectively examined, according to the results of which and histological examination, the patients were divided into 2 groups: the main group — 54 patients with laparoscopically and histologically confirmed external genital endometriosis (EGE); the control group — 26 patients without EGE. Before laparoscopy, a blood sample was taken from all patients for a molecular-biological study of the expression of 10 microRNAs: miR-183, miR-125b, miR-126, miR-16, miR-15a, miR-200a, miR-20a, miR-21, miR-222 and miR-29b. Identification of the studied and normalizing RNAs (U6 RNA and 103a microRNA) was performed according to the method of Chen et al. The presented values of the expression of the studied microRNAs are given in the form of 2-ΔCt. The expression ratio is given in the form of 2-ΔCt (main)/2-ΔCt (control), if the expression in the group of patients with endometriosis exceeded that in the control group, and in the form of 2-ΔCt (control)/2-ΔCt (main), if vice versa. Results . Comparison of the expression of 10 mi-croRNAs between the two groups revealed statistically significant differences only in miR-183: its expression in patients with EGE was statistically 1.5 times higher than that in women of the control group (p=0.017). We have not detected a difference in the expression of mir-200a, while according to other researchers, representatives of the mir-200 family are among the most frequent whose expression changes with endometriosis. MIR-16 expression also did not differ statistically among the patients we examined, whereas a group of American colleagues revealed its increase in patients with endometriosis and with endometriosis-associated ovarian tumors. We found no difference in mir-21 expression. The results of other researchers are contradictory: some found its increase in endometrioid cysts compared with eutopic endometrium, an increase in the epithelium of the fallopian tubes with their endometriosis compared with unaffected; others did not reveal a difference between the eutopic endometrium of endometriosis patients and healthy women, but showed a decrease in expression in peritoneal foci and foci of deep infiltrative endometriosis compared with eutopic endometrium. The expression of mir-222 was reduced in the patients we examined with endometriosis, which goes against the existing ideas about the pro-oncogenic role of this microRNA. An increase in its expression in cancer of the stomach, bladder, liver, lungs, breast, endometrium, ovaries is described. At the same time, the oncosuppressive effect of mir-222 is also known in prostate cancer, squamous cell carcinoma of the oral cavity. Conclusion . Taking into account the revealed statistically significant difference in microRNA expression by ROC analysis, we determined their effectiveness and specificity in the diagnosis of EGE. Of course, further studies with a large contingent of patients are needed to confirm the diagnostic value of these biomarkers. In addition, our study did not allow us to establish a statistical difference in microRNA expression in patients with impaired fertility. But it is the test that makes it possible to differentiate female infertility — associated with endometriosis and without it, as a rule, tubal-peritoneal genesis — that will become a key tool in the personalized management of patients with infertility. In our work, the distribution of patients by stages of EGE turned out to be uneven (there were no women with stage I at all) and it was not possible to establish a statistical difference in microRNA expression depending on the "length of service" of the disease.

Chronic lymphocytic leukemia (CLL) is the most common human leukemia. The disease is caused by abnormal proliferation and development of lymphocytes and their precursors in the blood and bone marrow (BM). Recent studies have shown that the CLL’s clinical course and outcome depend not only on genetic but also epigenetic factors. MicroRNAs (miRNAs) are involved in the development of hematological tumors, including CLL. The aim of this study is to identify the miRNA expression profile in CLL and determine the role of miRNAs in biological pathways associated with leukemogenesis in CLL. The following samples were used in this study: (1) samples obtained by sternal puncture and aspiration biopsy of BM (n = 115). They included samples from 21 CLL patients with anemia and indications for therapy and 45 CLL patients without anemia and with indications for therapy. The control group for the CLL BM samples consisted of patients with non-cancerous blood diseases (n = 35). (2) Lymph node (LN) samples (n = 20) were collected from CLL patients. The control group for the CLL LN samples consisted of patients with lymphadenopathy (n = 37). All cases were patients before treatment. We demonstrated a significant upregulation of miRNA-34a and miRNA-150 in CLL BM samples (p < 0.05) and downregulation of miRNA-451a in CLL LN samples (p < 0.05). We noted a dynamic increase in the levels of miRNA-150 and miRNA-34a in BM at various stages of tumor progression of CLL. We concluded that a dynamic picture of clinical manifestations of CLL closely correlates with changes in epigenetic characteristics of the tumor. Progression of the lymphoproliferative process and indications for cytoreductive therapy are associated with changes in the miRNA profile generated by cancer cells in different sites of clonal expansion.

Aim. This study aims to determine the frequency of solitary villous adenomas by colon segment and to compare the molecular genetic features of villous adenomas with the mucosa of the indexed segment and between different colon segments, as well as to consider the characteristics of unchanged mucosa of similar colon segments.Methods. A continuous cross-sectional retrospective study of 3,086 colonoscopy results was performed. In the study, 347 cellular specimens were analysed, including 109 villous adenomas, 101 index segment mucosa samples and 137 normal mucosa samples. Detection of miRNAs and mRNAs was conducted using real-time PCR. Somatic mutations were identified with allele-specific PCR and a hydrolysable probe.Results. The overall frequency of villous adenomas in the structure of all detected epithelial neoplasms was 3%. The frequency of villous adenomas was predominant in the sigmoid colon, while in other segments of the colon their frequency did not differ significantly. The frequency of severe dysplasia was associated with the adenoma diameter. Gene mutations similar to changes in villous adenomas were detected in the mucosa of index segments in the rectum, sigmoid colon and descending colon. Evaluation of the relative expression of 9 miRNAs and 9 protein-coding genes associated with the development of CRC in the mucosa of index segments and similar mucosal segments without adenomas did not reveal significant differences. The medians of relative expression levels of the most relevant markers – NOX1, LGR5, S4A12, TIMP, Ki-67, and TERT genes, as well as miRNA-135b, -20a, -21, -31, and -34a – were compared between different colon sections.Conclusion. The results suggest that inspecting and biopsying unchanged mucosa, even within the index segment, does not provide insight into the risk of developing villous adenoma.

Background: Molecular genetic events are among the numerous factors affecting the clinical course of papillary thyroid carcinoma (PTC). Recent studies have demonstrated that aberrant expression of miRNA, as well as different thyroid-related genes, correlate with the aggressive clinical course of PTC and unfavorable treatment outcome, which opens up new avenues for using them in personalization of the treatment strategy for patients with PTC. In the present work, our goal was to assess the applicability of molecular markers in preoperative diagnosis of aggressive variants of papillary thyroid cancer. Methods: The molecular genetic profile (expression levels of 34 different markers and BRAF mutation) was studied for 108 cytology specimens collected by fine-needle aspiration biopsy in patients with PTC having different clinical manifestations. Results: Statistically significant differences with adjustment for multiple comparisons (p < 0.0015) for clinically aggressive variants of PTC were obtained for four markers: miRNA-146b, miRNA-221, FN1, and CDKN2A. Weak statistical correlation (0.0015< р<0.05) was observed for miRNA-31, -375, -551b, -148b, -125b, mtDNA, CITED1, TPO, HMGA2, CLU, NIS, SERPINA1, TFF3, and TMPRSS4. Conclusions: The recurrence risk of papillary thyroid carcinoma can be preoperatively predicted using miRNA-221, the fibronectin and cyclin-dependent kinase inhibitor 2A genes.

Introduction. A great success of modern oncohematology is the achievement of remission with timely initiation of chemotherapy regimen in 80–85% of patients with Hodgkin lymphoma (HL). However, the problem of the occurrence of severe therapy-related toxic complications of specific therapy in this group of patients remains relevant. Micro¬RNAs (miRs) affect the maturation and differentiation of mesenchymal cells, including bone marrow cells, can play a key role in the activity of normal hematopoiesis and hematopoietic tumors, and also regulate the activity of gene metabolism of anticancer drugs. Aim. To determine the relationship between the miRNA expression in tumor biopsy samples of lymph nodes in patients with HL at the onset of the disease and the development of hematological toxicity during chemotherapy. Materials and methods. In accordance with the Common Terminology Criteria for Adverse Events v5.0, hematological toxicity was assessed in 40 patients with HL treated with the ABVD (n = 13) and BEACOPP (n = 27) chemotherapy regimens. The real-time polymerase chain reaction was used to determine the expression of 20 miRNAs in tumor biopsy samples of lymph nodes in all patients with HL before chemotherapy and in histological preparations of patients (n = 40) with reactive lymphadenopathy (RL) as a control group. Results. Toxic myelosuppression increased from the 1st to the 6th cycle of chemotherapy in patients treated with both the ABVD and BEACOPP regimens (p < 0.05). At the same time, grade 3–4 hematological toxicity in patients with HL treated with the BEACOPP regimen occurred 3 times more often than in patients with ABVD (p < 0.05), which indicates greater toxicity of the BEACOPP regimen. Overexpression of let-7c-5p, miR-185-5p and miR-128-3p positively correlates with the development of moderate and severe anemia (p < 0.05) in patients with HL after chemotherapy, suppressing the processes of maturation and differentiation of bone marrow cells, as well as activating their apoptosis. Conclusion. Determining the miRNA expression as molecular genetic predictors of the development of chemotherapy-related organ toxicity in patients with HL will help achieve appropriate treatment results, reducing the risks of adverse effects and maintaining a high quality of life for patients after chemotherapy.

Aim: to determine the prevalence of single non-villous adenomas in various segments of the colon and compare the segment-specific expression profiling of 9 genes and 9 microRNAs (miRNAs) between different tissue types, including single non-villous adenomas, the corresponding index segment mucosa, and the normal mucosa of similar segments from patients without adenomas. Materials and Methods: a retrospective analysis of 3086 colonoscopy results performed between 2019 and 2020 was conducted to assess the distribution of colonic adenomas. Additionally, a prospective study (2022–2023) was conducted involving 111 patients with non-villous adenomas. Biopsies were obtained from each segment of the colon, utilizing samples for the preparation of smears and histology. Relative expression levels of 9 miRNAs associated with colorectal cancer (CRC) were quantified in the collected smears. The selected miRNAs included miRNA-135b-5p, -141-3p, -143-3p, -200a-3p, -20a-5p, -21-5p, -31-5p, -34a-5p, and -92a-3p, with small nuclear RNA U6 (snRNA U6) and two reference miRNAs (miRNA-16-5p and -191-5p) used for normalization. Furthermore, expression levels of mRNA transcripts for 9 key protein-coding genes (MUC2, CDX2, NOX1, LGR5, SMAD4, MS4A12, TIMP1, Ki-67, and TERT) were assessed with normalization against the housekeeping genes PGK1 and PUM1. A total of 372 cell samples were analyzed, including 92 samples from adenomas, 111 from the mucosa of the index segments, and 169 from normal mucosa derived from patients without adenomas. Results: the majority of the detected single adenomas were non-villous adenomas, but their distribution across colon segments varied significantly (χ2=17.6, p<0.001). There were also notable differences in the frequency and types of somatic mutations in the BRAF and KRAS genes, along with the microsatellite instability (MSI) / microsatellite stability (MSS) status in different colon segments (χ2=6.0, p=0.014). Pairwise comparisons of miRNA/mRNA expression profiles showed no significant differences between the mucosa of the index segments and normal mucosa from patients without adenomas. However, the expression patterns of protein-coding genes, including LGR5, TIMP1, MS4A12, and Ki-67, varied across colon segments. These expression patterns were consistently altered in both mucosa with adenomas and normal mucosa, with the exception of the caecum and rectum. Conclusion: this study identified significant differences in the prevalence and mutation frequency of single non-villous adenomas across colon segments. However, comparison of somatic mutations, MSI status, and miRNA/mRNA expression profiles between index segment mucosa and analogous normal mucosa suggests comparable molecular characteristics, with exceptions noted in the cecum and rectum. These findings challenge the widely-accepted model of adenomas as strict precursors to CRC. Keywords: non-villous adenomas, colorectal cancer, miRNA/mRNA expression, microsatellite instability, protein-coding genes. For citation: Korotkevich A.G., Zhilina N.M., Demenkov P.S., Veryaskina Yu.A., Titov S.E. Comparative segmental assessment of the colon mucosa in non-villous adenomas. RMJ. 2024;10:9–17. DOI: 10.32364/2225-2282-2024-10-2

Background/Objectives: A modern classification distinguishes between two nosological entities posing an intermediate risk between differentiated and anaplastic carcinoma: poorly differentiated thyroid carcinoma and differentiated high-grade thyroid carcinoma. There are currently few studies searching for the preoperative molecular genetic markers of high-grade papillary thyroid carcinoma (PTC HG), primarily because of a recent WHO reclassification and singling out of a separate entity: high-grade follicular cell-derived nonanaplastic thyroid carcinoma. Therefore, this work was aimed at identifying PTC HG-specific microRNAs and mRNAs that reliably distinguish them from differentiated papillary thyroid carcinoma in preoperative cytology specimens (fine-needle aspiration biopsies). Methods: A molecular genetic profile (expression levels of 14 genes and eight microRNAs) was studied in 110 cytology specimens from patients with PTC: 13 PTCs HG and 97 PTCs without features of HG. Results: Of the examined eight microRNAs and 14 genes, significant differences in the expression levels between the PTC and PTC HG groups were revealed for genes SLC26A7, TFF3, and TPO. Only one gene (SLC26A7) proved to be crucial for detecting PTC HG. It showed the largest area under the ROC curve (0.816) in differentiation between the PTC and PTC HG groups and was the key element of the decision tree by ensuring 54% sensitivity and 87.6% specificity. Conclusions: Early preoperative diagnosis of PTC HG in patients with early stages of this cancer type will allow clinicians to modify a treatment strategy toward a larger surgery volume and lymph node dissection and may provide indications for subsequent radioactive iodine therapy.

Multiple myeloma (MM) is characterized by the uncontrolled proliferation of monoclonal plasma cells and accounts for approximately 10% of all hematologic malignancies. The clinical outcomes of MM can exhibit considerable variability. Variability in both the genetic and epigenetic characteristics of MM undeniably contributes to tumor dynamics. The aim of the present study was to identify biomarkers with the potential to improve the accuracy of prognosis assessment in MM. Initially, miRNA sequencing was conducted on bone marrow (BM) samples from patients with MM. Subsequently, the expression levels of 27 microRNAs (miRNA) and the gene expression levels of ASF1B, CD82B, CRISP3, FN1, MEF2B, PD-L1, PPARγ, TERT, TIMP1, TOP2A, and TP53 were evaluated via real-time reverse transcription polymerase chain reaction in BM samples from patients with MM exhibiting favorable and unfavorable prognoses. Additionally, the analysis involved the bone marrow samples from patients undergoing examinations for non-cancerous blood diseases (NCBD). The findings indicate a statistically significant increase in the expression levels of miRNA-124, -138, -10a, -126, -143, -146b, -20a, -21, -29b, and let-7a and a decrease in the expression level of miRNA-96 in the MM group compared with NCBD (p < 0.05). No statistically significant differences were detected in the expression levels of the selected miRNAs between the unfavorable and favorable prognoses in MM groups. The expression levels of ASF1B, CD82B, and CRISP3 were significantly decreased, while those of FN1, MEF2B, PDL1, PPARγ, and TERT were significantly increased in the MM group compared to the NCBD group (p < 0.05). The MM group with a favorable prognosis demonstrated a statistically significant decline in TIMP1 expression and a significant increase in CD82B and CRISP3 expression compared to the MM group with an unfavorable prognosis (p < 0.05). From an empirical point of view, we have established that the complex biomarker encompassing the CRISP3/TIMP1 expression ratio holds promise as a prognostic marker in MM. From a fundamental point of view, we have demonstrated that the development of MM is rooted in a cascade of complex molecular pathways, demonstrating the interplay of genetic and epigenetic factors.

Introduction. Primary cutaneous T cell lymphomas (CTCL) are a heterogeneous group of extranodal non-Hodgkin’s lymphomas that are locally limited to the skin at diagnosis. The diagnosis of CTCL is often difficult, since at certain stages of development, this hematological malignancy has clinical similarities with non-neoplastic dermatological diseases such as chronic eczematous dermatitis, psoriasis, lichen ruber, or fungal infections. Both genetic and epigenetic factors, in particular microRNAs (miRNAs), are involved in the pathogenesis of CTCL. Aim. To identify the miRNAs that differentiate CTCL from benign skin lesions (BSL) and determine their role in genetic pathways involved in the development of CTCL. Materials and methods. Real-time reverse transcription PCR was used to analyze the expression levels of miRNA-181a, -155, -574, -148b, -191, -26a, -21, -124, -221, -200b, -20a, -92a, -145, let-7a, and let-7d in 5 formalin-fixed paraffin-embedded skin biopsy samples from patients with CTCL and 20 skin biopsy samples from patients with psoriasis (control group). Introduction. Primary cutaneous T cell lymphomas (CTCL) are a heterogeneous group of extranodal non-Hodgkin’s lymphomas that are locally limited to the skin at diagnosis. The diagnosis of CTCL is often difficult, since at certain stages of development, this hematological malignancy has clinical similarities with non-neoplastic dermatological diseases such as chronic eczematous dermatitis, psoriasis, lichen ruber, or fungal infections. Both genetic and epigenetic factors, in particular microRNAs (miRNAs), are involved in the pathogenesis of CTCL. Aim. To identify the miRNAs that differentiate CTCL from benign skin lesions (BSL) and determine their role in genetic pathways involved in the development of CTCL. Materials and methods. Real-time reverse transcription PCR was used to analyze the expression levels of miRNA-181a, -155, -574, -148b, -191, -26a, -21, -124, -221, -200b, -20a, -92a, -145, let-7a, and let-7d in 5 formalin-fixed paraffin-embedded skin biopsy samples from patients with CTCL and 20 skin biopsy samples from patients with psoriasis (control group). Results. Comparative analysis of miRNA expression levels between CTCL and BSL samples showed a statistically significant increase in the levels of miRNA-181a, -155, -574, -148b and -191 in tumor samples (p < 0.05). ROC analysis showed that miRNA-155 and miRNA-181a are highly sensitive and specific markers for the diagnosis of CTCL. Conclusion. Analysis of miRNA expression levels may be a promising tool for the differential diagnosis between dermatotropic lymphoid hematological malignancies and non-hematological skin diseases.

Hodgkin’s lymphomas (HL) and the majority of non-Hodgkin’s lymphomas (NHL) derive from different stages of B-cell differentiation. MicroRNA (miRNA) expression profiles change during lymphopoiesis. Thus, miRNA expression analysis can be used as a reliable diagnostic tool to differentiate tumors. In addition, the identification of miRNA’s role in lymphopoiesis impairment is an important fundamental task. The aim of this study was to analyze unique miRNA expression profiles in different types of B-cell lymphomas. We analyzed the expression levels of miRNA-18a, -20a, -96, -182, -183, -26b, -34a, -148b, -9, -150, -451a, -23b, -141, and -128 in lymph nodes (LNs) in the following cancer samples: HL (n = 41), diffuse large B-cell lymphoma (DLBCL) (n = 51), mantle cell lymphoma (MCL) (n = 15), follicular lymphoma (FL) (n = 12), and lymphadenopathy (LA) (n = 37), as well as bone marrow (BM) samples: HL (n = 11), DLBCL (n = 42), MCL (n = 14), FL (n = 16), and non-cancerous blood diseases (NCBD) (n = 43). The real-time RT-PCR method was used for analysis. An increase in BM expression levels of miRNA-26b, -150, and -141 in MCL (p < 0.01) and a decrease in BM levels of the miR-183-96-182 cluster and miRNA-451a in DLBCL (p < 0.01) were observed in comparison to NCBD. We also obtained data on increased LN levels of the miR-183-96-182 cluster in MCL (p < 0.01) and miRNA-18a, miRNA-96, and miRNA-9 in FL (p < 0.01), as well as decreased LN expression of miRNA-150 in DLBCL (p < 0.01), and miRNA-182, miRNA-150, and miRNA-128 in HL (p < 0.01). We showed that miRNA expression profile differs between BM and LNs depending on the type of B-cell lymphoma. This can be due to the effect of the tumor microenvironment.

This study unpacks how leader humility and charisma are related to leader effectiveness and satisfaction with the leader and examines how the need for leadership may moderate these relationships. We used data from 252 respondents from Russian companies in a 2 (high vs. low leader charisma) × 2 (high vs. low leader humility) vignette design in which levels of charisma and humility were manipulated. While leader humility was found to have a positive effect on satisfaction with a leader, no significant link between leader humility and leader effectiveness was observed in this study. Leader charisma was positively related to leader effectiveness and satisfaction with the leader. The interaction between leader charisma and leader humility in relation to leadership outcomes was found to be positive and significant. The need for leadership did not affect the relations between leader charisma and leader humility on the one hand and outcome variables on the other hand. However, the need for leadership did show strong positive relations with both leader effectiveness and satisfaction with the leader. The study's findings suggest that leader humility increases prosocial orientation and cooperation between the leaders and followers leading to higher satisfaction with the leaders. Leader charisma may motivate the subordinate more, resulting in greater (perceived) effectiveness of the leader and increasing satisfaction with the leader. Leader charisma and humility can interact, reinforcing higher leadership outcomes. Though results are based on a single cultural context, investigating the interaction between leader charisma and leader humility with leadership outcomes offers implications for theory and practice.

Digital transformation (DT) is a complex, socio-technical, strategic, and often radical change influenced by various aspects, among which non-technological, organizational factors play significant roles. The literature on DT enablers suggests sensitivity to the organizational context, especially to the technology intensity of companies. This article analyzes the variations in non-technological DT enablers in high-tech and low-tech manufacturing companies. Through a systematic literature review, using coding techniques and cluster analysis, we created 20 aggregated enabler categories. With the Decision Making Trial and Evaluation Laboratory (DEMATEL) method, clustered DT enablers in high-tech and low-tech companies were compared. High-tech companies enable DT with the factors related primarily to organizational flexibility and dynamism. In contrast, low-tech firms propel DT with the enablers connected to more stable, traditional, managerial practices. JEL Classification: 031 and 032

Disturbed cervicovaginal-microbiome (CVM) structure promotes human papillomavirus (HPV) persistence and reflects risks of cervical lesions and cancer onset and recurrence. Therefore, microbiomic biomarkers may be useful for cervical disease screening and patient management. Here, by 16S rRNA gene sequencing and commercial PCR-based diagnostic kits, we profiled CVM in cytological preparations from 140 HPV-tested women (from Novosibirsk, Russia) with normal cytological findings, cervical lesions, or cancer and from 101 women who had recently received different cancer therapies. An increase in lesion severity was accompanied by higher HPV prevalence and elevated CVM biodiversity. Post-treatment CVM was found to be enriched with well-known microbial biomarkers of dysbiosis, just as in cervical disease. Nonetheless, concentrations of some skin-borne and environmental species (which gradually increased with increasing lesion severity)-especially Cutibacterium spp., Achromobacter spp., and Ralstonia pickettii-was low in post-treatment patients and depended on treatment types. Frequency of Lactobacillus iners dominance was high in all groups and depended on treatment types in post-treatment patients. Microbiome analysis via PCR-based kits revealed statistically significant differences among all groups of patients. Thus, microbiome profiling may help to find diagnostic and prognostic markers for management of cervical lesions; quantitative PCR-based kits may be suitable for these purposes.

Non-Hodgkin lymphoma (NHL) is a heterogeneous group of cancers that differ in pathogenesis and prognosis. The main methods of treating NHL include chemotherapy, immunochemotherapy, and radiation therapy. However, a significant proportion of these tumors are chemoresistant or rapidly recur after a short chemotherapy-induced remission. In this regard, the search for alternative cytoreductive therapeutic methods is relevant. Aberrant expression of microRNA (miRNA) is one of the mechanisms responsible for the emergence and progression of malignant lymphoid neoplasms. We analyzed the profile of miRNA expression in the biopsy material from lymph nodes affected by diffuse large B-cell lymphoma (DLBCL). The key material of the study was histological preparations of lymph nodes obtained by excisional diagnostic biopsy and treated using conventional histomorphological formalin fixation methods. The study group consisted of patients with DLBCL (n = 52); the control group consisted of patients with reactive lymphadenopathy (RL) (n = 40). It was shown that the miR-150 expression level in DLBCL was reduced by more than 12 times (p = 3.6 x 10(-15)) compared with RL. Bioinformatics analysis revealed the involvement of miR-150 in the regulation of hematopoiesis and lymphopoiesis. The data we obtained allow us to consider miR-150 as a promising therapeutic target with great potential in clinical practice.

Introduction. Follicular thyroid cancer is much less common than papillary cancer. Nevertheless, the main difficulties in preoperative diagnosis are associated with this morphological type. A fine needle aspiration biopsy is not able to distinguish a benign follicular adenoma from a follicular carcinoma, which forces surgeons to perform diagnostic resection of the thyroid gland in all patients with a cytological conclusion «follicular tumor». Aim. To search for microRNAs specific to follicular cancer by sequencing a new generation. Materials and methods. The data of patients with a preoperative cytological conclusion «follicular tumor» operated at the Chelyabinsk Center for Endocrine Surgery from 2021 to 2022 were analyzed. Histological preparations were reviewed twice by pathologists. Genome sequencing was performed in 8 histological samples of follicular cancer and 8 samples of follicular adenoma. The expression levels of the selected microRNAs were compared with 198 archived cytological samples of various types of thyroid tumors. Results. The risk of malignancy at the cytological conclusion «follicular tumor» was 25.4 % (error 74.6 %). Follicular cancer was first detected in 36 patients, the incidence was 0.68 new cases per 100 thousand population per year. The diagnosis of «follicular cancer» was confirmed by 3 morphologists in 8 (36.4 %) cases. Sequencing revealed the 5 most distinct microRNAs between follicular cancer and follicular adenoma: miR-625, miR-323a, let-7a, let-7c and miR-574. The level of errors in the differentiation of follicular adenoma and follicular cancer using the microRNAs we selected was 21 % (35 % with cross-validation). Conclusion. Molecular genetic research at the preoperative stage, aimed at differentiating follicular cancer and follicular adenoma, in comparison with cytological research has a greater, but insufficient accuracy for making a final clinical decision.