College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, P.R. China.
Cancer Center, Weifang Traditional Chinese Hospital, Weifang, Shandong 261000, P.R. China.
Mol Med Rep. 2019 Jan;19(1):362-374. doi: 10.3892/mmr.2018.9636. Epub 2018 Nov 9.
Chronic lymphocytic leukemia (CLL) is a malignant clonal proliferative disorder of B cells. Inhibition of cell apoptosis and cell cycle arrest are the main pathological causes of this disease, but its molecular mechanism requires further investigation. The purpose of the present study was to identify biomarkers for the early diagnosis and treatment of CLL, and to explore the molecular mechanisms of CLL progression. A total of 488 differentially expressed genes (DEGs) and 32 differentially expressed microRNAs (miRNAs; DEMs) for CLL were identified by analyzing the gene chips GSE22529, GSE39411 and GSE62137. Functional and pathway enrichment analyses of DEGs demonstrated that DEGs were mainly involved in transcriptional dysregulation and multiple signaling pathways, such as the nuclear factor‑κB and mitogen‑activated protein kinase signaling pathways. In addition, Cytoscape software was used to visualize the protein‑protein interactions of these DEGs in order to identify hub genes, which could be used as biomarkers for the early diagnosis and treatment of CLL. Cytoscape software was also used to analyze the association between the predicted target mRNAs of DEMs and DEGs and increase knowledge about the miRNA‑mRNA regulatory network associated with the progression of CLL. Taken together, the present study provided a bioinformatics basis for advancing our understanding of the pathogenesis of CLL by identifying differentially expressed hub genes, miRNA‑mRNA target pairs and molecular pathways. In addition, hub genes may be used as novel biomarkers for the diagnosis of CLL and to guide the selection of CLL drug combinations.
慢性淋巴细胞白血病(CLL)是一种 B 细胞恶性克隆性增殖性疾病。细胞凋亡抑制和细胞周期停滞是该病的主要病理原因,但分子机制尚需进一步研究。本研究旨在寻找 CLL 的早期诊断和治疗的生物标志物,并探讨 CLL 进展的分子机制。通过分析基因芯片 GSE22529、GSE39411 和 GSE62137,鉴定出 488 个差异表达基因(DEGs)和 32 个差异表达 microRNA(miRNA;DEMs)用于 CLL。DEGs 的功能和通路富集分析表明,DEGs 主要参与转录失调和多种信号通路,如核因子-κB 和丝裂原激活蛋白激酶信号通路。此外,使用 Cytoscape 软件可视化这些 DEGs 的蛋白质-蛋白质相互作用,以鉴定出可能作为 CLL 早期诊断和治疗的生物标志物的枢纽基因。还使用 Cytoscape 软件分析了 DEMs 和 DEGs 的预测靶 mRNA 与 DEGs 之间的关联,增加了对与 CLL 进展相关的 miRNA-mRNA 调控网络的了解。综上所述,本研究通过鉴定差异表达的枢纽基因、miRNA-mRNA 靶对和分子通路,为深入了解 CLL 的发病机制提供了生物信息学基础。此外,枢纽基因可作为 CLL 诊断的新型生物标志物,并指导 CLL 药物组合的选择。