乳腺良恶性疾病DNA双链断裂的定量分析

G. Smagulova, M. Aitmagambetova, G. V. Veklenko, N. Kereeva, A. Zheksenova, A. Amanzholkyz, A. Tulyaeva, G. Bakytzhanov
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摘要

相关性:双链DNA断裂是最危险的DNA损伤。磷酸化组蛋白H2AX (γH2AX)的焦点分析是目前检测DNA双链断裂最敏感的方法。这种蛋白修饰可以成为细胞应激的生物标志物,特别是在诊断和监测肿瘤疾病方面。在这项研究中,我们利用新颖的模式识别算法在AKLIDES®平台上自动分析γ - h2ax焦点的免疫荧光图像,并将结果与视觉评分进行比较。研究了乳腺癌和乳腺良性肿瘤患者外周血单个核细胞γ - h2ax灶的形成。本文旨在量化乳腺癌和乳腺良性肿块患者外周血淋巴细胞DNA双链断裂,以确定可能的生物标志物。方法:采用自动AKLIDES系统对29例乳腺癌患者和24例乳腺良性肿瘤患者淋巴细胞中γ-H2AX灶进行分析。结果:主、对照组骨折通道“FITC”指标比较,“Foci dia”指标(p=0.0382)、“Focilnt mean”指标(p=0.0166)、“Colocalisation”指标(p=0.0486)差异有统计学意义。在修复通道“AРС”中,“nucleus BGInt”指标(p=0.0166)和“Focilnt mean”指标(p=0.0118)存在显著差异。结论:各组与对照组间FITC断裂通道DNA双链断裂及APC修复的变化可能作为乳腺癌的诊断标志。
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QUANTIFICATION OF DNA DOUBLE-STRAND BREAKS IN BENIGN AND MALIGNANT BREAST DISEASES
Relevance: Double-strand DNA breaks are the most dangerous DNA damage. Analysis of foci of phosphorylated histone protein H2AX (γH2AX) is currently the most sensitive method for detecting DNA double-strand breaks. This protein modification can become a biomarker of cellular stress, especially in diagnosing and monitoring neoplastic diseases. In this study, we utilized novel pattern recognition algorithms on the AKLIDES® platform to automatically analyze immunofluorescent images of γH2AX foci and compare the results with visual scores. The γH2AX foci formation on peripheral blood mononuclear cells of women with breast cancer or benign breast tumors was studied. The article aimed to quantify DNA double-strand breaks in peripheral blood lymphocytes in women with breast cancer and benign breast masses to identify a possible biomarker. Methods: γ-H2AX foci in lymphocytes were analyzed using the automated AKLIDES system in patients with breast cancer (n=29) and benign breast tumors (n=24). Results: When comparing the indicators of the main and control groups in the channel of ruptures “FITC,” a statistically significant difference was found in the indicators “Foci dia” (p=0.0382), “Focilnt mean” (p=0.0166), “Colocalisation” (p=0.0486). In the repair channel “AРС,” significant differences were found in the indicators “Nuclei BGInt” (p=0.0166) and the indicator “Focilnt mean” (p=0.0118). Conclusion: The revealed changes of DNA double-strand breaks along the FITC break channels and APC repair between the main and control groups can possibly serve as a breast cancer diagnostic marker.
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