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系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种免疫性性疾病。乳腺癌(breast cancer,BC)即乳腺恶性肿瘤,是女性常见的恶性肿瘤之一。乳腺癌患者体内众多免疫功能低下,其免疫系统无法识别并杀死癌细胞,然而,系统性红斑狼疮患者体内免疫系统反应过度强烈,产生大量抗体攻击自身细胞,可见两种疾病均与免疫系统息息相关但调控结果背道而驰,目前这一机制尚不明确。基于此,本研究从基因之间的关联性考虑,首先,利用互信息(mutual information,MI)方法筛选出1 250个SLE与BC共有显著基因;第二,将这些基因利用David分析,得到37个转录因子及其调控的378个靶基因,最后,采用快速网络成分分析算法(fast network component analysis,Fast NCA)分别预测SLE和BC发病过程中转录因子活性以及对靶基因调控强度的变化,并构建调控网络。经过两种疾病调控网络对比,发现AKT2、CCAR1、MTF2、RUFY2等基因在这两种疾病中活性变化明显相反,并且通过分子生物学分析,它们在有丝分裂,细胞凋亡,免疫反应以及炎症反应过程中的变化对SLE与BC的致病具有重要作用。
Systemic lupus erythematosus (SLE) is an autoimmune disease. Breast cancer (breast cancer, BC) is a malignant breast cancer, is one of the common malignant tumors in women. However, the immune system in patients with systemic lupus erythematosus over-intense reaction to produce a large number of antibodies to attack their own cells, showing that both diseases are closely linked with the immune system However, the results of regulation run counter to the current mechanism is not yet clear. Based on this, this study considered the relationship between genes, first of all, the use of mutual information (mutual information, MI) method screened 1250 SLE and BC shared significant genes; second, the analysis of these genes using David, 37 And 378 target genes regulated by them. Finally, the fast network component analysis (Fast NCA) was used to predict the transcription factor activity and the regulation of the target genes in SLE and BC Build regulatory network. After comparing the two disease control networks, it was found that the activities of AKT2, CCAR1, MTF2, RUFY2 and other genes are oppositely changed in the activity of these two diseases, and they are in the process of mitosis, apoptosis, immune reaction and inflammatory reaction through molecular biology analysis The changes in the SLE and BC pathogenesis has an important role.