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: 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.
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 per cent, 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 purpose was to find specific diagnostic markers by methylation profiling of peripheral blood mononuclear fraction DNA in breast cancer patients. Results: Plasma samples of the Kazakhstani population with breast cancer possessed mononuclear fraction methylation markers in CpG islets associated with JAM3, C17orf64, MSC, and C7orf51 genes and the CpG islet associated with the intragenic region of the 5, chr5: 77,208,034-77,329,434 chromosome, 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 fraction DNA methylation profile, namely in CpG islets associated with JAM3, C17orf64, MSC, and C7orf51 genes and the CpG islet associated with the intragenic region of the 5, chr5: 77,208,034-77,329,434 chromosome is enough specific and sensitive to use it in breast cancer screening
Актуальность: Доброкачественная патология молочных желез во всем мире встречается приблизительно у 80% женщин репродуктивного возраста. Различные виды мастопатии расцениваются врачами как факторы риска развития онкологического заболевания, так как у 3-6% пациенток они трансформируется в рак молочной железы. В настоящее время нет единой общепринятой тактики лечения данной патологии, так как заболевание может протекать по-разному на фоне тех или иных сопутствующих патологий или гормонального дисбаланса в организме. Поэтому вылечить мастопатию можно не только хирургическим способом. Одним из основных методов лечения данной патологии является медикаментозное, которое основывается на приеме препаратов, направленных первым долгом на урегулировании гормонального фона. Однако до настоящего времени отсутствует единая тактика лечения заболевания и не существуют утвержденных общепринятых рекомендаций по лечению мастопатии. Цель исследования: На основании анализа данных литературных источников оценить эффективность и безопасность использования лекарственного препарата BNO 1025, содержащего экстракт Vitex аgnus сastus (VAC), при лечении дисгормональных нарушений молочных желез. Методы исследования: обзор опубликованных результатов научных и клинических исследований по базе данных PubMed за период 2010-2021 гг. Результаты: Проанализированные результаты исследований, представленных в литературе, показывают, что препарат BNO 1025 при фиброзно-кистозной мастопатии проявляет достаточный уровень клинической эффективности при благоприятном профиле безопасности и имеет определенное преимущество над биологически активными добавками. Заключение: Данные РКИ демонстрируют высокую эффективность лечения VAC при доброкачественной дисгормональной дисфункции молочных желез. На сегодняшний день данный препарат является препаратом выбора у женщин фертильного возраста при первичной и повторной монотерапии. Тем не менее, считаем необходимым более тщательно разработать дизайн РКИ для определения оптимальной продолжительности лечения препаратом BNO 1025, уточнения эффективности различных дозировок и подтверждения результатов с использованием различных стандартизированных экстрактов VAC.
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