Bai Wenxiang, Wang Honghua, Bai Hua
Comprehensive Cancer Center, Xiangshui People's Hospital, Xiangshui 224600, People's Republic of China.
Department of Respiratory Medicine, Xiangshui People's Hospital, Xiangshui, 224600, People's Republic of China.
Pharmgenomics Pers Med. 2019 Dec 31;12:387-396. doi: 10.2147/PGPM.S228574. eCollection 2019.
Systemic amyloid light chain (AL) amyloidosis is a rare plasma cell disease. However, the regulatory mechanisms of AL amyloidosis have not been thoroughly uncovered, identification of candidate genes and therapeutic agents for this disease is crucial to provide novel insights into exploring the regulatory mechanisms underlying AL amyloidosis.
The gene expression profile of GSE73040, including 9 specimens from AL amyloidosis patients and 5 specimens from normal control, was downloaded from GEO datasets. Differentially expressed genes (DEGs) were sorted with regard to AL amyloidosis versus normal control group using Limma package. The gene enrichment analyses including GO and KEGG pathway were performed using DAVID website subsequently. Furthermore, the protein-protein interaction (PPI) network for DEGs was constructed by Cytoscape software and STRING database. DEGs were mapped to the connectivity map datasets to identify potential molecular agents of AL amyloidosis.
A total of 1464 DEGs (727 up-regulated, 737 down-regulated) were identified in AL amyloidosis samples versus control samples, these dysregulated genes were associated with the dysfunction of ribosome biogenesis and immune response. PPI network and module analysis uncovered that several crucial genes were defined as candidate genes, including and . More importantly, we identified the small molecular agents (AT-9283, Ritonavir and PKC beta-inhibitor) as the potential drugs for AL amyloidosis.
Using bioinformatics approach, we have identified candidate genes and pathways in AL amyloidosis, which can extend our understanding of the cause and molecular mechanisms, and these crucial genes and pathways could act as biomarkers and therapeutic targets for AL amyloidosis.
系统性轻链（AL）淀粉样变性是一种罕见的浆细胞疾病。然而，AL淀粉样变性的调控机制尚未完全阐明，鉴定该疾病的候选基因和治疗药物对于深入探索AL淀粉样变性的调控机制至关重要。
从GEO数据集中下载GSE73040的基因表达谱，其中包括9例AL淀粉样变性患者的样本和5例正常对照的样本。使用Limma软件包对AL淀粉样变性组与正常对照组的差异表达基因（DEG）进行分类。随后使用DAVID网站进行基因富集分析，包括基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析。此外，利用Cytoscape软件和STRING数据库构建DEG的蛋白质-蛋白质相互作用（PPI）网络。将DEG映射到连接图谱数据集以鉴定AL淀粉样变性的潜在分子药物。
在AL淀粉样变性样本与对照样本中总共鉴定出1464个DEG（727个上调，737个下调），这些失调的基因与核糖体生物合成功能障碍和免疫反应相关。PPI网络和模块分析发现几个关键基因被定义为候选基因，包括……和……。更重要的是，我们鉴定出小分子药物（AT-9283、利托那韦和蛋白激酶Cβ抑制剂）作为AL淀粉样变性的潜在药物。
通过生物信息学方法，我们在AL淀粉样变性中鉴定出候选基因和通路，这可以扩展我们对其病因和分子机制的理解，并且这些关键基因和通路可作为AL淀粉样变性的生物标志物和治疗靶点。
