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通过加权基因共表达网络分析确定葡萄膜黑色素瘤诊断的特征基因。

Identify the signature genes for diagnose of uveal melanoma by weight gene co-expression network analysis.

作者信息

Shi Kai, Bing Zhi-Tong, Cao Gui-Qun, Guo Ling, Cao Ya-Na, Jiang Hai-Ou, Zhang Mei-Xia

机构信息

Department of Ophthalmology, West China Hospital, Sichuan University, Chendu 610041, Sichuan Province, China ; Molecular Medicine Research Center, West China Hospital, Sichuan University, Chendu 610041, Sichuan Province, China.

Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, Gansu Province, China.

出版信息

Int J Ophthalmol. 2015 Apr 18;8(2):269-74. doi: 10.3980/j.issn.2222-3959.2015.02.10. eCollection 2015.

Abstract

AIM

To identify and understand the relationship between co-expression pattern and clinic traits in uveal melanoma, weighted gene co-expression network analysis (WGCNA) is applied to investigate the gene expression levels and patient clinic features. Uveal melanoma is the most common primary eye tumor in adults. Although many studies have identified some important genes and pathways that were relevant to progress of uveal melanoma, the relationship between co-expression and clinic traits in systems level of uveal melanoma is unclear yet. We employ WGCNA to investigate the relationship underlying molecular and phenotype in this study.

METHODS

Gene expression profile of uveal melanoma and patient clinic traits were collected from the Gene Expression Omnibus (GEO) database. The gene co-expression is calculated by WGCNA that is the R package software. The package is used to analyze the correlation between pairs of expression levels of genes. The function of the genes were annotated by gene ontology (GO).

RESULTS

In this study, we identified four co-expression modules significantly correlated with clinic traits. Module blue positively correlated with radiotherapy treatment. Module purple positively correlates with tumor location (sclera) and negatively correlates with patient age. Module red positively correlates with sclera and negatively correlates with thickness of tumor. Module black positively correlates with the largest tumor diameter (LTD). Additionally, we identified the hug gene (top connectivity with other genes) in each module. The hub gene RPS15A, PTGDS, CD53 and MSI2 might play a vital role in progress of uveal melanoma.

CONCLUSION

From WGCNA analysis and hub gene calculation, we identified RPS15A, PTGDS, CD53 and MSI2 might be target or diagnosis for uveal melanoma.

摘要

目的

为了识别并理解葡萄膜黑色素瘤中共表达模式与临床特征之间的关系,应用加权基因共表达网络分析(WGCNA)来研究基因表达水平和患者临床特征。葡萄膜黑色素瘤是成人中最常见的原发性眼肿瘤。尽管许多研究已经确定了一些与葡萄膜黑色素瘤进展相关的重要基因和通路,但在系统水平上葡萄膜黑色素瘤中共表达与临床特征之间的关系仍不清楚。在本研究中,我们采用WGCNA来研究分子与表型之间的潜在关系。

方法

从基因表达综合数据库(GEO)收集葡萄膜黑色素瘤的基因表达谱和患者临床特征。基因共表达通过WGCNA(R软件包)计算。该软件包用于分析基因表达水平对之间的相关性。通过基因本体论(GO)对基因功能进行注释。

结果

在本研究中,我们确定了四个与临床特征显著相关的共表达模块。蓝色模块与放射治疗呈正相关。紫色模块与肿瘤位置(巩膜)呈正相关,与患者年龄呈负相关。红色模块与巩膜呈正相关,与肿瘤厚度呈负相关。黑色模块与最大肿瘤直径(LTD)呈正相关。此外,我们在每个模块中确定了枢纽基因(与其他基因连接性最高)。枢纽基因RPS15A、PTGDS、CD53和MSI2可能在葡萄膜黑色素瘤进展中起关键作用。

结论

通过WGCNA分析和枢纽基因计算,我们确定RPS15A、PTGDS、CD53和MSI2可能是葡萄膜黑色素瘤的治疗靶点或诊断标志物。

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