乳腺癌的放射敏感性与circ-HIPK3、circ-PVT1、miR-25和miR-149的表观遗传调控有关。
Epigenetic regulation of circ-HIPK3, circ-PVT1, miR-25, and miR-149 in radiosensitivity of breast cancer.
发表日期:2023 Aug 01
作者:
Elahe Abdollahi, Hossein Mozdarani
来源:
Epigenetics & Chromatin
摘要:
评估放射疗法(RT)之前细胞的放射敏感性可以帮助选择适当的治疗方案,减少接受放射暴露的患者中不良副作用的发生率。在本研究中,我们收集了来自已被诊断为浸润性导管癌乳腺癌(IDC)的60名女性的血样。患者的平均年龄为47 ± 9.93岁。此外,该研究还包括20名健康女性,平均年龄为44.43 ± 6.7岁。使用标准G2测定法进行预测细胞对辐射的反应。在60个样本中,G2测定法确定了20名乳腺癌患者表现出放射敏感性。因此,最终在两个包含各20名对象的等价队列中进行了分子调查,其中一个具有细胞放射敏感性,另一个则没有。使用定量聚合酶链反应(qPCR)评估了周围血单核细胞(PBMCs)中miR-149、miR-25、circ-PVT1和circ-HIPK3的表达水平。使用受试者工作特征(ROC)曲线评估了RNA的敏感性和特异性。进行二元logistic回归分析,以研究RNAs与BC和BC患者中的细胞放射敏感性(CR)之间的关系。结果显示,被诊断为BC的个体中circ-HIPK3和circ-PVT1明显上调。circ-HIPK3和circ-PVT1的水平与BC患者的CR直接相关。ROC曲线的分析表明,circ-HIPK3和circ-PVT1在准确预测BC和BC患者的CR方面具有良好的特异性和敏感性。二元logistic回归分析的结果表明,circ-HIPK3和circ-PVT1是预测BC和CR的有效指标。ROC曲线和二元logistic回归分析的结果表明,miR-25是仅适用于BC患者的可靠预测指标。我们的研究表明,circ-HIPK3、circ-PVT1和miR-25可能参与BC的调控过程。循环RNA circ-HIPK3、circ-PVT1以及miR-25等重要生物标志物有望成为预测BC的良好指标。此外,circ-HIPK3和circ-PVT1有潜力成为预测BC患者的CR的生物标志物。版权所有 © 2023。Elsevier Inc. 发表。
Assessing the radiosensitivity of cells before administering radiation therapy (RT) to individuals diagnosed with breast cancer (BC) can facilitate the selection of appropriate treatment regimens and minimize the incidence of adverse side effects in patients undergoing radiation exposure. In this research, blood samples were obtained from 60 women who had been diagnosed with Invasive Ductal Carcinoma (IDC) Breast Cancer. The average age of the patients was 47 ± 9.93. Additionally, the study incorporated 20 healthy women, with an average age of 44.43 ± 6.7. A standard G2 assay was conducted to predict the cellular response to radiation. Out of the 60 samples, the G2 assay identified 20 patients with breast cancer who exhibited radiosensitivity. Hence, molecular investigations were ultimately conducted on two equivalent cohorts comprising 20 subjects each, one with and the other without cellular radiosensitivity. The expression levels of miR-149, miR-25, circ-PVT1, and circ-HIPK3 in peripheral blood mononuclear cells (PBMCs) were evaluated using quantitative polymerase chain reaction (qPCR). Receiver Operating Characteristic (ROC) curves were used to evaluate the sensitivity and specificity of the RNAs. An analysis using binary logistic regression was performed to investigate the relationship between RNAs and both BC and cellular radiosensitivity (CR) in patients with BC. The findings revealed a significant upregulation of Circ-HIPK3 and circ-PVT1 in individuals diagnosed with BC. The levels of Circ-HIPK3 and Circ-PVT1 were found to be directly associated with CR in BC patients. The analysis of the ROC curve demonstrated that circ-HIPK3 and circ-PVT1 exhibit favorable specificity and sensitivity in accurately predicting both BC and CR in patients with BC. The findings from the binary logistic regression analysis demonstrated that circ-HIPK3 and circ-PVT1 were effective predictors of both BC and CR. The ROC curve and binary logistic regression analyses provide evidence that miR-25 is a reliable predictor for BC patients exclusively. Our research has demonstrated that circ-HIPK3, circ-PVT1, and miR-25 may be involved in BC regulatory processes. The circular RNAs Circ-HIPK3 and circ-PVT1, as well as miR-25, among other significant biomarkers, could potentially serve as promising biomarkers for predicting BC. Furthermore, Circ-HIPK3 and circ-PVT1 have the potential to serve as biomarkers for predicting CR in BC patients.Copyright © 2023. Published by Elsevier Inc.