关键词: bioinformatic methods differentially expressed genes pheochromocytoma and paraganglioma prognostic markers tumor-infiltrating immune cells

Mesh : Adrenal Gland Neoplasms / genetics metabolism pathology Adrenal Glands / metabolism Biomarkers, Tumor / genetics metabolism Gene Regulatory Networks Humans Paraganglioma / genetics metabolism pathology Pheochromocytoma / genetics metabolism pathology Protein Interaction Maps Survival Analysis Transcriptome

来  源:   DOI:10.1266/ggs.20-00057

Abstract:
The pathogenesis of pheochromocytoma and paraganglioma (PCPG) catecholamine-producing tumors is exceedingly complicated. Here, we sought to identify important genes affecting the prognosis and survival rate of patients suffering from PCPG. We analyzed 95 samples obtained from two microarray data series, GSE19422 and GSE60459, from the Gene Expression Omnibus (GEO) repository. First, differentially expressed genes (DEGs) were identified by comparing 87 PCPG tumor samples and eight normal adrenal tissue samples using R language. The GEO2R tool and Venn diagram software were applied to the Database for Annotation, Visualization and Integrated Discovery (DAVID) to analyze Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO). We further employed Cytoscape with the Molecular Complex Detection (MCODE) tool to make protein-protein interactions visible for the Search Tool for Retrieval of Interacting Genes (STRING). These procedures resulted in 30 candidate DEGs, which were subjected to Kaplan-Meier analysis and validated by Gene Expression Profiling Interactive Analysis (GEPIA) to determine their influence on overall survival rate. Finally, we identified ALDH3A2 and AKR1B1, two genes in the glycerolipid metabolism pathway, as being particularly enriched in PCPG tumors and correlated with T and B tumor-infiltrating immune cells. Our results suggest that these two DEGs are closely associated with the prognosis of malignant PCPG tumors.
摘要:
嗜铬细胞瘤和副神经节瘤(PCPG)产生儿茶酚胺的肿瘤的发病机制非常复杂。这里,我们试图鉴定影响PCPG患者预后和生存率的重要基因.我们分析了从两个微阵列数据系列中获得的95个样本,GSE19422和GSE60459,来自基因表达综合(GEO)库。首先,通过使用R语言比较87个PCPG肿瘤样品和8个正常肾上腺组织样品来鉴定差异表达基因(DEGs)。将GEO2R工具和维恩图软件应用于注释数据库,可视化和集成发现(DAVID)分析京都百科全书的基因和基因组(KEGG)途径和基因本体论(GO)。我们进一步使用Cytoscape与分子复合物检测(MCODE)工具,以使蛋白质-蛋白质相互作用对于检索相互作用基因的搜索工具(STRING)可见。这些程序产生了30个候选DEG,对其进行Kaplan-Meier分析,并通过基因表达谱交互分析(GEPIA)进行验证,以确定其对总体生存率的影响。最后,我们确定了ALDH3A2和AKR1B1,这两个基因在甘油脂代谢途径中,在PCPG肿瘤中特别富集,并与T和B肿瘤浸润性免疫细胞相关。我们的结果表明,这两个DEGs与恶性PCPG肿瘤的预后密切相关。
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