Background Breast cancer (BC) is the most common cancer among women worldwide. At present, there is a need to search for new, accurate, reliable, minimally invasive and cheap biomarkers in addition to existing methods for the diagnosis and prognosis of BC. The main goal of this study was to test the diagnostic value of six circulating miRNAs in Kazakh women. Materials and methods TaqMan-based miRNA profiling was conducted using plasma specimens from 35 BC women patients and 33 healthy women samples (control group). Results The level of all seven miRNAs (including endogenous control) normalized by synthetic cel-miR-39 were significantly elevated in the group of BC patients. Normalization using miR-222-3p as endogenous control reduced differences in level of miRNAs between groups; as a result, only three miRNAs were significantly upregulated in the group of BC patients—miR-145-5p (P = 6.5e−12), miR-191-5p (P = 3.7e−10) and miR-21-5p (P = 0.0034). Moreover, ROC analysis showed that the use of miR-145-5p and miR-191-5p, both individually (AUC = 0.931 and 0.904, respectively) or in combination (AUC = 0.984), allows to accurately differentiate BC patients from healthy individuals. Conclusions Two plasma miRNAs—miR-145-5p and miR-191-5p—are potential biomarkers for diagnosis of BC in the Kazakh population. The findings need to be further substantiated using a more representative sample.

Relevance: According to the International Agency for Research on Cancer (IARC), lung cancer (LC) currently ranks first in cancer incidence and mortality worldwide. The gold standard of LC diagnostics is the histological verification, the determination of the degree of invasion and tumor phenotype. At first glance, epigenetic methods seem to be secondary after determining the patient’s genetic profile. However, standard genetic analysis reveals only the DNA nucleotide sequence. Thus, epigenetic analysis is the only method that allows detecting potential abnormalities in cells. An important difference between genetic and epigenetic changes is that drugs are efficient against epigenetic changes but absolutely powerless against genetic mutations. The purpose of the study was to review and analyze the available molecular genetic methods for DNA methylation profiling in lung cancer. Results: All these observations support the hypothesis that methylation profiling in body fluids can help determine the people predisposed to or affected by LC. Circulating acellular DNA in the blood plasma contains tumor-specific mutations and disease-related DNA methylation patterns. Identifying new biomarkers-precursors of a potential cancer susceptibility or aggressiveness in such DNA would be a considerable advancement in prognostic medicine for patients at high risk of developing LC. Conclusion: A low level of LC detection might limit the number of DNA samples of patients with LC included in the studies. This is also the reason why specific methylation biomarkers have not yet been confirmed for clinical use. Future research on a larger number of blood samples, combined with the entire epigenome studies, may contribute to finding a group of LC biomarkers to improve LC detection.

Relevance: COVID-19 impacts the course of cancer depending on the status and volume of cancer patient vaccination against COVID-19. The study aimed to assess the impact of accelerated high-tech radiation therapy on the course of the oncological process, depending on the status and volume of COVID-19 vaccinations. Methods: This quantitative and qualitative prospective randomized controlled scientific study was conducted as part of the implementation of the scientific project, “Innovative approach to managing patients with cancer in the context of the COVID pandemic-19,” Reg. No. AP13068657. The study involved 221 cancer patients. Results: COVID-19 was diagnosed in 54/221 (24.4%) of the study participants, 24 (22.4%) in the standard radiotherapy group, and 30 (26.3%) in the experimental radiotherapy group. 49/221 (22.2%) of the participants were vaccinated. COVID-19 was detected in one breast cancer patient in the experimental group (1.5%) two months after vaccination and two patients with prostate cancer (2.4%) four months after vaccination. Relapse-free survival was registered in 59 (85.5%) breast cancer patients in the standard group and 58 (85.3%) in the experimental group. The overall survival of breast cancer patients was 69 (100.0%) in the standard group and 68 (97.0%) in the experimental group. Relapse-free survival was registered in 32 (84.2%) prostate cancer patients in the standard group and 41 (89.1%) patients in the experimental group. The overall survival among prostate cancer patients was 34 (89.5%) in the standard group and 45 (97.8%) in the experimental group. The deaths were not related to COVID-19. The average treatment duration for breast cancer was less by 12.9 days, with prostate cancer– by 18.2 days. Conclusion: In Kazakhstan, 4.8% of cancer patients with COVID-19 died in 2020-2021. The use of accelerated high-tech radiotherapy is justified in the context of the COVID-19 pandemic. Vaccination can prevent COVID-19 development in cancer patients.

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Relevance: According to the International Agency for Research on Cancer (IARС), breast cancer ranks 1st-2nd among other cancers globally [1], including Kazakhstan [2]. In Kazakhstan, the annual growth in breast cancer incidence exceeds 26.6%. In 2018-2019, breast cancer was the 3rd most common cause of cancer death in Kazakhstan, accounting for 8.7-8.1 percent, respectively. Early detection of breast cancer remains an acute issue. In particular, early detection should be improved. Epigenetic studies of cancer patients confirm that epigenetic biomarkers could be used as early cancer diagnostic markers, including breast cancer. The study aimed to find specific diagnostic markers by methylation profiling of peripheral blood mononuclear cell (PBMC) DNA in breast cancer patients. Results: Plasma samples of the Kazakhstani population with breast cancer possessed mononuclear cell methylation markers in CpG islets associated with JAM3, C17orf64, MSC, and C7orf51 genes and the CpG islet associated with the intergenic region on chromosome 5, chr5: 77,208,034-77,329,434, which were missing in healthy individuals. These biomarkers allow differentiating breast cancer from other cancers with a specificity of 0.91 and a sensitivity of 0.94 compared to methylation data from open DNA methylation databases (for Illumina 450K): TCGA, GSE40279, GSE61496, GSE76269 и GSE66836. Conclusion: Early breast cancer detection method using peripheral blood mononuclear cell DNA methylation profile, namely in CpG islets associated with JAM3, C17orf64, MSC, and C7orf51 genes and the CpG islet associated with the intergenic region on chromosome 5, chr5: 77,208,034-77,329,434 is enough specific and sensitive to use it in breast cancer screening.

Breast cancers with heterogeneous HER2 amplification show a diverse distribution of 'driver' and 'passenger' somatic mutations and copy number variations

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