Wang Ping, Yang Xuan, Zhou Nan, Wang Jinyuan, Li Yang, Liu Yueming, Xu Xiaolin, Wei Wenbin
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.
Onco Targets Ther. 2020 Nov 19;13:11923-11934. doi: 10.2147/OTT.S280435. eCollection 2020.
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 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 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.
葡萄膜黑色素瘤（UM）是成人原发性眼内肿瘤，肝转移率很高。识别潜在的关键基因可为UM转移的早期检测和预后提供信息。
使用GSE22138数据集鉴定差异表达基因（DEG）。采用加权基因共表达网络分析构建共表达模块。对DEG和关键模块的基因进行功能富集分析。通过共表达网络和蛋白质-蛋白质相互作用网络（PPI）筛选枢纽基因，并在癌症基因组图谱数据库中通过生存分析进行验证。使用基因集富集分析（GSEA）探索UM的潜在转移机制。采用瞬时转染研究金属蛋白酶组织抑制因子1（TIMP1）对UM细胞增殖、迁移和侵袭的影响。
共鉴定出原发性和转移性UM之间的552个DEG，主要富集于细胞外基质、细胞衰老和粘着斑途径。构建加权基因共表达网络以识别与UM转移相关的关键基因模块（n = 36）。绿松石模块与转移呈正相关，该模块中的基因主要富集于肽基酪氨酸自磷酸化和器官生长调节。通过共表达网络和PPI分析筛选出枢纽基因。GSEA显示TIMP1高表达与p53途径相关且总生存时间短。实验结果表明，TIMP1过表达抑制UM细胞的增殖和迁移，但对其侵袭无显著影响。
我们的研究表明，[此处原文缺失具体基因名称]可能与UM转移有关，这可能对识别转移高危患者和预测UM预后具有重要意义。
