Identification of key genes and pathways in seminoma by bioinformatics analysis
Identification of key genes and pathways in seminoma by bioinformatics analysis
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DOI：
10.2147/ott.s199115
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发表时间：
2019-01-01
影响因子：
4
通讯作者：
Xu, Ning
中科院分区：
文献类型：
--
作者：
Chen, Ye-Hui;Lin, Ting-Ting;Xu, Ning
背景：精原细胞瘤占睾丸生殖细胞肿瘤病例的大部分，睾丸生殖细胞肿瘤是 15 至 44 岁男性中最常见的恶性肿瘤。了解肿瘤发生的分子机制对于更好的临床诊断和治疗具有重要意义。目的：我们进行生物信息学分析，以更好地在基因水平上了解精原细胞瘤，并探索用于诊断、治疗和预后的潜在候选基因或分子。方法：对包含40个精原细胞瘤样本和3个健康睾丸样本的基因表达谱（GSE8607）进行分析以进行差异识别 与精原细胞瘤发生相关的表达基因（DEG）。然后使用基因本体论和京都基因百科全书和基因组通路富集分析进行功能注释。使用 Cytoscape 和用于检索相互作用基因的搜索工具构建 DEG 的蛋白质-蛋白质相互作用 (PPI) 网络并选择中心基因。此外，对这些枢纽基因进行了表达水平验证和总体生存的Kaplan-Meier分析。结果：在精原细胞瘤和健康样本之间总共鉴定了1,636个DEG，其中701个在精原细胞瘤中上调，这些DEG在免疫反应、防御反应、受体活性和信号转导活性的调节方面富集；第935章 在精原细胞瘤中下调，并与生殖过程、激酶活性和碳水化合物衍生物结合相关。根据连接程度从PPI网络中选择5个中心基因：IL6、VEGFA、IL10、CCR5和CXCR4。其中，CCR5和CXCR4的高表达水平与精原细胞瘤患者的不良预后相关。从 PPI 网络中选择的四个模块表明，精原细胞瘤与 Janus 激酶信号转导器和转录信号通路激活剂、趋化因子信号通路、内吞作用和细胞因子-细胞因子受体相互作用有关。结论：这些鉴定的 DEG 和枢纽基因有助于我们了解精原细胞瘤的潜在分子机制，并有可能用于诊断 精原细胞瘤的生物标志物或治疗靶点。
Background: Seminoma accounts for the most part of cases of testicular germ cell tumor, which is the most common malignancy among males between ages 15 and 44 years. Understanding the molecular mechanism of tumorigenesis is important for better clinical diagnosis and treatment.Purpose: We performed bioinformatics analysis to better understand seminoma at the genetic level and to explore potential candidate genes or molecules for diagnosis, treatment, and prognosis.Methods: A gene expression profile (GSE8607), containing 40 seminoma samples and three healthy testes samples, was analyzed to identify differentially expressed genes (DEGs) associated with the occurrence of seminoma. Functional annotation was then performed using gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Cytoscape with Search Tool for the Retrieval of Interacting Genes was used to construct a protein-protein interaction (PPI) network of the DEGs and select hub genes. Moreover, validation of expression level and Kaplan-Meier analysis for overall survival were conducted to those hub genes.Results: A total of 1,636 DEGs were identified between seminoma and healthy samples, including 701 up-regulated in seminoma that were enriched in the regulation of immune responses, defense responses, receptor activity, and signal transducer activity; 935 were down-regulated in seminoma and were associated with reproductive processes, kinase activity, and carbohydrate derivative binding. Five hub genes were selected from the PPI network according to the degree of connectivity: IL6, VEGFA, IL10, CCR5, and CXCR4. Among them, high expression levels of CCR5 and CXCR4 were associated with poor prognosis for seminoma patients. Four modules selected from the PPI network revealed that seminoma was connected with the Janus kinase-signal transducers and activators of transcription signaling pathway, chemokine signaling pathway, endocytosis, and cytokine-cytokine receptor interaction.Conclusion: These identified DEGs and hub genes facilitate our knowledge of the underlying molecular mechanism of seminoma and have the potential to be used as diagnostic biomarkers or therapeutic targets for seminoma.