Key Laboratory for Experimental Teratology of Ministry of Education, Department of Histology & Embryology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, Shandong, China.
School of Information Engineering, Zhengzhou University, Zhengzhou, 450001, Henan, China.
BMC Cancer. 2022 Jan 3;22(1):5. doi: 10.1186/s12885-021-09070-2.
Intrahepatic cholangiocarcinoma (ICC) is a type of malignant tumor ranking the second in the incidence of primary liver cancer following hepatocellular carcinoma. Both the morbidity and mortality have been increasing in recent years. Small duct type of ICC has potential therapeutic targets. But overall, the prognosis of patients with ICC is usually very poor.
To search latent therapeutic targets for ICC, we programmatically selected the five most suitable microarray datasets. Then, we made an analysis of these microarray datasets (GSE26566, GSE31370, GSE32958, GSE45001 and GSE76311) collected from the Gene Expression Omnibus (GEO) database. The GEO2R tool was effective to find out differentially expressed genes (DEGs) between ICC and normal tissue. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were executed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) v 6.8. The Search Tool for the Retrieval of Interacting Genes (STRING) database was used to analyze protein-protein interaction of these DEGs and protein-protein interaction of these DEGs was modified by Cytoscape3.8.2. Survival analysis was performed using Gene Expression Profiling Interactive Analysis (GEPIA) online analysis tool.
A total of 28 upregulated DEGs and 118 downregulated DEGs were screened out. Then twenty hub genes were selected according to the connectivity degree. The survival analysis results showed that A2M was closely related to the pathogenesis and prognosis of ICC and was a potential therapeutic target for ICC.
According to our study, low A2M expression in ICC compared to normal bile duct tissue was an adverse prognostic factor in ICC patients. The value of A2M in the treatment of ICC needs to be further studied.
肝内胆管癌(ICC)是原发性肝癌中仅次于肝细胞癌的第二大恶性肿瘤类型。近年来,ICC 的发病率和死亡率一直在上升。小胆管型 ICC 具有潜在的治疗靶点。但总体而言,ICC 患者的预后通常非常差。
为了寻找 ICC 的潜在治疗靶点,我们通过编程选择了五个最合适的微阵列数据集。然后,我们对这些从基因表达综合数据库(GEO)收集的微阵列数据集(GSE26566、GSE31370、GSE32958、GSE45001 和 GSE76311)进行了分析。GEO2R 工具可有效用于找出 ICC 和正常组织之间的差异表达基因(DEGs)。使用数据库注释、可视化和综合发现(DAVID)v6.8 对基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析进行了分析。使用 Search Tool for the Retrieval of Interacting Genes(STRING)数据库来分析这些 DEGs 的蛋白质-蛋白质相互作用,并通过 Cytoscape3.8.2 修改这些 DEGs 的蛋白质-蛋白质相互作用。使用在线分析工具基因表达谱交互分析(GEPIA)进行生存分析。
筛选出 28 个上调 DEGs 和 118 个下调 DEGs。然后,根据连接度选择了 20 个枢纽基因。生存分析结果表明,A2M 与 ICC 的发病机制和预后密切相关,是 ICC 的潜在治疗靶点。
根据我们的研究,与正常胆管组织相比,ICC 中 A2M 的低表达是 ICC 患者不良预后的一个危险因素。A2M 在 ICC 治疗中的价值需要进一步研究。