Liu Guozhen, Hu Xiaoling, Gao Lei, Feng Zhenjun
Department of Hematology, People's Hospital of Liaocheng, Liaocheng, Shandong, China (mainland).
Med Sci Monit. 2017 May 6;23:2159-2167. doi: 10.12659/msm.900738.
BACKGROUND B cell chronic lymphocytic leukemia (B-CLL) is the most common adult leukemia in the Western world. Although therapeutic advances have notably improved the outcome for many patients, B-CLL remains an incurable disease. The purpose of this study was to search for therapeutic drugs based on altered pathways in individual patients. MATERIAL AND METHODS Genes from microarray data were mapped to 300 Homo sapiens-related pathways. Individual pathway aberrance analysis was used to identify altered pathways. Drug data, obtained from connectivity map (cMAP), were subjected to drug-set enrichment analysis. To analyze the relations between drug-induced pathways and disease-induced altered pathways in individuals, Pearson correlation analysis was applied. RESULTS The disease-induced pathways with P-values <0.05 in individual samples were recorded and presented in a heatmap. Drug-induced pathways were analyzed in the 104 samples. After Pearson correlation analysis between altered pathways and drug, the 20 top-ranked drugs that were most relevant to disease were obtained. There were 9 drugs with positive scores and 11 with negative scores. CONCLUSIONS With this method, we identified the 20 top-ranked drugs that were most relevant to disease. The drugs with negative scores may play therapeutic roles in B-CLL.
背景 B细胞慢性淋巴细胞白血病(B-CLL)是西方世界最常见的成人白血病。尽管治疗进展显著改善了许多患者的预后,但B-CLL仍然是一种无法治愈的疾病。本研究的目的是根据个体患者中改变的信号通路寻找治疗药物。
材料与方法 来自微阵列数据的基因被映射到300条与智人相关的信号通路。使用个体信号通路异常分析来识别改变的信号通路。从连接图谱(cMAP)获得的药物数据进行药物集富集分析。为了分析个体中药物诱导的信号通路与疾病诱导的改变的信号通路之间的关系,应用了Pearson相关分析。
结果 记录了个体样本中P值<0.05的疾病诱导信号通路,并以热图形式呈现。在104个样本中分析了药物诱导的信号通路。在改变的信号通路与药物之间进行Pearson相关分析后,获得了与疾病最相关的排名前20的药物。有9种药物得分为正,11种得分为负。
结论 通过这种方法,我们确定了与疾病最相关的排名前20的药物。得分阴性的药物可能在B-CLL中发挥治疗作用。