He Guangyao, Tang Anzhou, Xie Mao, Xia Wei, Zhao Pengcheng, Wei Jianglian, Lai Yongjing, Tang Xianglong, Zou Yi Ming, Liu Heng
Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Department of Mathematical Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
Dose Response. 2020 Mar 30;18(1):1559325820914184. doi: 10.1177/1559325820914184. eCollection 2020 Jan-Mar.
Radiotherapy is an effective treatment for local solid tumors, but the mechanism of damage to human body caused by radiation therapy needs further study. In this study, gene expression profiles of human peripheral blood samples exposed to different doses and rates of ionizing radiation (IR) were used for bioinformatics analysis to investigate the mechanism of IR damage and radiation-induced bystander effect (RIBE). Differentially expressed genes analysis, weighted gene correlation network analysis, functional enrichment analysis, hypergeometric test, gene set enrichment analysis, and gene set variation analysis were applied to analyze the data. Moreover, receiver operating characteristic curve analysis was performed to identify core genes of IR damage. Weighted gene correlation network analysis identified 3 modules associated with IR damage, 2 were positively correlated and 1 was negatively correlated. The analysis showed that the positively correlated modules were significantly involved in apoptosis and p53 signaling pathway, and ESR1, ATM, and MYC were potential transcription factors regulating these modules. Thus, the study suggested that apoptosis and p53 signaling pathway may be the potential molecular mechanisms of IR damage and RIBE, which could be driven by ESR1, ATM, and MYC.
放射治疗是治疗局部实体瘤的一种有效方法，但放疗对人体造成损伤的机制仍需进一步研究。在本研究中，利用暴露于不同剂量和剂量率电离辐射（IR）的人外周血样本的基因表达谱进行生物信息学分析，以探究IR损伤机制及辐射旁效应（RIBE）。采用差异表达基因分析、加权基因共表达网络分析、功能富集分析、超几何检验、基因集富集分析和基因集变异分析对数据进行分析。此外，通过绘制受试者工作特征曲线分析来鉴定IR损伤的核心基因。加权基因共表达网络分析确定了3个与IR损伤相关的模块，其中2个呈正相关，1个呈负相关。分析表明，正相关模块显著参与细胞凋亡和p53信号通路，ESR1、ATM和MYC是调节这些模块的潜在转录因子。因此，该研究提示细胞凋亡和p53信号通路可能是IR损伤和RIBE的潜在分子机制，且可能由ESR1、ATM和MYC驱动。
