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Identifying a Potential Key Gene, TIMP1, Associated with Liver Metastases of Uveal Melanoma by Weight Gene Co-Expression Network Analysis.

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机构: [1]Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophthalmology & Visual Sciences Key Lab, Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People’s Republic of China
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关键词: weighted gene co-expression network analysis WGCNA uveal melanoma liver metastases GO analysis pathway analysis

摘要:
Uveal melanoma (UM) is a primary intraocular tumor in adults, with a high percentage of metastases to the liver. Identifying potential key genes may provide information for early detection and prognosis of UM metastasis.Differentially expressed genes (DEGs) were identified using the GSE22138 dataset. Weighted gene co-expression network analysis was used to construct co-expression modules. Functional enrichment analysis was performed for DEGs and genes of key modules. Hub genes were screened by co-expression network and protein-protein interaction network (PPI), and validated by survival analysis in The Cancer Genome Atlas database. Gene set enrichment analysis (GSEA) was used to explore the potential metastasis mechanism of UM. Transient transfection was used to investigate the effect of TIMP1 on the proliferation, migration, and invasion of UM cells.In total, 552 DEGs were identified between primary and metastatic UM and mainly enriched in extracellular matrix, cellular senescence and focal adhesion pathway. A weighted gene co‑expression network was built to identify key gene modules associated with UM metastasis (n=36). The turquoise module is positively correlated with metastasis and genes in this module were mainly enriched in peptidyl-tyrosine autophosphorylation and regulation of organ growth. The hub gene TIMP1 was screened out by co-expression network and PPI analysis. High expression of TIMP1 was related to p53 pathway by GSEA and short overall survival time. Experimental results indicated that overexpression of TIMP1 inhibited the proliferation and migration, while it had no significant effect on invasion of UM cells.Our study indicates that TIMP1 might be associated with metastasis in UM, which might have important significance for identifying patients with high risk of metastasis and predicting the prognosis of UM.© 2020 Wang et al.

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出版当年[2019]版:
大类 | 3 区 医学
小类 | 3 区 生物工程与应用微生物 4 区 肿瘤学
最新[2023]版:
大类 | 4 区 医学
小类 | 3 区 生物工程与应用微生物 4 区 肿瘤学
第一作者:
第一作者机构: [1]Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophthalmology & Visual Sciences Key Lab, Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People’s Republic of China
通讯作者:
通讯机构: [1]Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophthalmology & Visual Sciences Key Lab, Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People’s Republic of China [*1]Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophthalmology & Visual Sciences Key Lab, Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People’s Republic of China
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