Colorectal cancer (CRC) is a common cancer worldwide. The main cause of death in CRC includes tumor progression and metastasis. At molecular level, these processes may be triggered by epithelial-mesenchymal transition (EMT) and necessitates specific alterations in cell metabolism. Although several EMT-related metabolic changes have been described in CRC, the mechanism is still poorly understood. Using CrossHub software, we analyzed RNA-Seq expression profile data of CRC derived from The Cancer Genome Atlas (TCGA) project. Correlation analysis between the change in the expression of genes involved in glycolysis and EMT was performed. We obtained the set of genes with significant correlation coefficients, which included 21 EMT-related genes and a single glycolytic gene, HK3. The mRNA level of these genes was measured in 78 paired colorectal cancer samples by quantitative polymerase chain reaction (qPCR). Upregulation of HK3 and deregulation of 11 genes (COL1A1, TWIST1, NFATC1, GLIPR2, SFPR1, FLNA, GREM1, SFRP2, ZEB2, SPP1, and RARRES1) involved in EMT were found. The results of correlation study showed that the expression of HK3 demonstrated a strong correlation with 7 of the 21 examined genes (ZEB2, GREM1, TGFB3, TGFB1, SNAI2, TWIST1, and COL1A1) in CRC. Upregulation of HK3 is associated with EMT in CRC and may be a crucial metabolic adaptation for rapid proliferation, survival, and metastases of CRC cells.

Assessment of homologous recombination deficiency (HRD) status is now essential for ovarian cancer patient management. The aim of our study was to analyze the influence of ethnic variations, tumor purity, and neoadjuvant chemotherapy (CT) on the determination of HRD scores as well as to evaluate feasibility of HRD testing with the Amoy HRD Focus Assay in routine clinical practice. The HRD status, including the BRCA status and genomic scar score (GSS), was analyzed in 452 ovarian cancer specimens. The successful rate of HRD testing was 86% (388/452). The BRCA mutational rate was 29% (114/388); 252 samples (65%) were classified as HRD-positive. Our data demonstrate the feasibility of internal HRD testing by the AmoyDx HRD Focus Panel for high-grade serous ovarian cancer (HGSOC), showing results similar to other methods. The HRD rate in the Russian population is very similar to those of other European populations, as is the BRCA mutation frequency. The most substantial contribution to HRD level diversity is testing criteria depending on intrahospital arrangements. The analysis shows that biallelic BRCA alterations had higher GSS compared with those with monoallelic inactivation, consistent with positive HRD status. The study indicates that grades 1–2 of the pathological response caused by chemotherapy affect HRD scores and suggests controlling for tumor purity of 40% or more as a critical factor for GSS measurement.

CpG island methylator phenotype (CIMP) is found in 15–20% of malignant colorectal tumors and is characterized by strong CpG hypermethylation over the genome. The molecular mechanisms of this phenomenon are not still fully understood. The development of CIMP is followed by global gene expression alterations and metabolic changes. In particular, CIMP-low colon adenocarcinoma (COAD), predominantly corresponded to consensus molecular subtype 3 (CMS3, “Metabolic”) subgroup according to COAD molecular classification, is associated with elevated expression of genes participating in metabolic pathways. We performed bioinformatics analysis of RNA-Seq data from The Cancer Genome Atlas (TCGA) project for CIMP-high and non-CIMP COAD samples with DESeq2, clusterProfiler, and topGO R packages. Obtained results were validated on a set of fourteen COAD samples with matched morphologically normal tissues using quantitative PCR (qPCR). Upregulation of multiple genes involved in glycolysis and related processes (ENO2, PFKP, HK3, PKM, ENO1, HK2, PGAM1, GAPDH, ALDOA, GPI, TPI1, and HK1) was revealed in CIMP-high tumors compared to non-CIMP ones. Most remarkably, the expression of the PKLR gene, encoding for pyruvate kinase participating in gluconeogenesis, was decreased approximately 20-fold. Up to 8-fold decrease in the expression of OGDHL gene involved in tricarboxylic acid (TCA) cycle was observed in CIMP-high tumors. Using qPCR, we confirmed the increase (4-fold) in the ENO2 expression and decrease (2-fold) in the OGDHL mRNA level on a set of COAD samples. We demonstrated the association between CIMP-high status and the energy metabolism changes at the transcriptomic level in colorectal adenocarcinoma against the background of immune pathway activation. Differential methylation of at least nine CpG sites in OGDHL promoter region as well as decreased OGDHL mRNA level can potentially serve as an additional biomarker of the CIMP-high status in COAD.

Introduction. Nowadays the standard of care for locally advanced and metastatic urothelial carcinoma (UC) is a combination of platinum-based drugs. However, such a therapy is characterized with high toxicity and selective efficacy. So, the question of the optimal alternative to the first line of therapy and the choice of drugs for the second line of therapy is currently relevant.Immune checkpoint inhibitors have revolutionized the treatment of UC. Nevertheless, despite the fact that initially the drugs of this series showed a fairly high efficacy as a second-line therapy for metastatic UC, at present there is no unambiguous opinion about the correct tactics of their use. There is also no consensus on the predictive value of PD-L1 biomarkers and their significance in determining treatment tactics.Aim. To evaluate the efficacy and tolerability of first-line atezolizumab therapy in 22 patients with unresectable forms of UC.Materials and methods. The experience of the State Clinical Hospital named after D.D. Pletnev on the example of 22 patients with advanced UC who received first-line therapy with atezolizumab 1200 mg intravenously once every 21 days until progression or intolerable toxicity. Efficacy was assessed according to RECIST 1.1 criteria.Results and discussion. Median follow-up 16.3 months. The objective response rate (ORR) is estimated at 72.7%, 95% CI. A complete response according to RECIST 1.1 criteria was observed in 5 patients (22.7%). Median time to first response was 2.2 months (range 1.5-5.7), late responses (at 5 and 5.7 months) required space in 2 patients. Median progression-free survival was 5.2 months (95% CI) in all patients. Median overall survival (OS) 18.5 months (95% CI). Specific application-related events were required in 10 (45.4%) cases. All the side effects were managed by standard symptomatic therapy. The dosage of atezoli-zumab was reduced in 7 (32%) cases. Immune-mediated adverse events were reported in 5 (23%) patients. No patient received systemic non-corticosteroid immunomodulatory agents for immune-mediated events. 2 (9%) patients received corticosteroids.Conclusions. Atezolizumab has shown high efficacy in the first line of treatment for advanced UC.

Purpose of the study. Analytical review and analysis of available literature on texture analysis of computed tomgraphy (CT) and magnetic resonance imaging (MRI) in noninvasive diagnosis of ICC and correlation with molecular genetic features and tumor immunophenotype.Materials and methods. The scientific publications and clinical guidelines in the information- analytical systems PubMed, Scopus for 2012–2022 were carried out using the keywords: "mri", "radiomics", "texture analysis", "radiogenomics", "intrahepatic cholangiocarcinoma", "molecular". 49 articles were selected for analysis after excluding studies dealing with technical aspects of radiomics and describing individual clinical observations.Results. The presented review demonstrated the broad possibilities and prospects of application of CT and MRI texture analysis in the study of cholangiocellular cancer, including the first results in the study of molecular features (signatures) of this tumor. Correlation of texture features with the expression of immunotherapy target genes KRAS/NRAS/BRAF as well as IDH1/2 mutation was shown. Texture scores were the predominant independent predictor of microvascular invasion, which was a major independent risk factor for postoperative recurrence.Conclusion. The use of texture analysis undoubtedly demonstrates promising possibilities both in noninvasive assessment of the HCC histological differentiation grade, as well as in differential diagnosis with hepatocellular carcinoma, metastases, and requires further study for systematization and standardization of the obtained data.

Objective. Analysis of the results of treatment of patients with metastatic liver tumors using laser ablation. Material and methods. Results of treatment of 27 patients with metastatic liver lesions who underwent laser ablation for the period from March, 2017 to January 2023, were analyzed. The size of lesions was 10—40 mm, average size — 29.8±1.7 mm). Laser destruction was performed percutaneously, with laparoscopic and open approaches under ultrasound scanning in real time mode. For laser ablation, an ECHO LASER X4 device (Italy) was used. Ultrasound, MRI and CT with intravenous contrast were used for the dynamically control of ablation effectiveness. Results. In the early postoperative period, in one case, the formation of a subcapsular hematoma was observed in the area of the light guide, which did not require surgical intervention. The average bed/day was 4 days. One-year overall survival stood at 88%, two-year overall survival stood at 71%, 3-years — 43.5%. Conclusion. The use of laser ablation is indicated for insufficient functional liver volume in patients with previously extensive liver resections, and in somatically burdened patients who cannot undergo liver resection.