Identified IGSF9 association with prognosis and hypoxia in nasopharyngeal carcinoma by bioinformatics analysis.

Identified IGSF9 association with prognosis and hypoxia in nasopharyngeal carcinoma by bioinformatics analysis.
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通过生物信息学分析确定IGSF9与鼻咽癌预后和缺氧的相关性

DOI:
10.1186/s12935-020-01587-z
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发表时间:
2020
影响因子:
5.8
通讯作者:
Deng M
Deng M
中科院分区:
医学2区
文献类型:
--
作者:
Huang D;Liu Q;Zhang W;Huang C;Zheng R;Xie G;Wang H;Jia B;Shi J;Yuan Y;Deng M

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尽管鼻咽癌(NPC)的治疗有所改善,但复发和转移的患者预后仍然很差。因此,迫切需要鉴定新的生物标志物来预测NPC的结果和定制治疗。从Gene Expression Omnibus下载4个数据集,其中一个数据集GSE 68799通过构建共表达网络筛选关键模块和枢纽基因。其他数据集(GSE 12452和GSE 53819)用于验证枢纽基因。数据集GSE 102349致力于通过存活分析鉴定预后枢纽基因。为了探讨预后中枢基因是否与鼻咽癌的缺氧特征相关,进行了相关性分析,并随后进行了这些基因的体外功能验证实验。通过共表达网络分析,蓝色模块被认为是良性和恶性组中的关键模块,并且蓝色模块的IGSF 9被鉴定为预后枢纽基因。此外,IGSF 9的表达与3个标签(99-gene、26-gene和15-gene)的缺氧评分之间存在较强的相关性,有望成为鼻咽癌缺氧相关基因。进一步的功能研究证实IGSF 9的表达下调可降低鼻咽癌细胞的增殖、迁移和侵袭能力,缺氧可诱导IGSF 9的表达。IGSF 9与鼻咽癌的预后有关,并参与了缺氧的发生。IGSF 9有可能成为一种新的鼻咽癌预后指标。
Despite improvements in nasopharyngeal carcinoma (NPC) treatment, patients with recurrence and metastasis still have a poor prognosis. Thus, the identification of novel biomarkers is urgently needed to predict outcomes and tailor treatment for NPC. Four data sets were downloaded from Gene Expression Omnibus, and one data set GSE68799 of which was applied to filtrate key modules and hub genes by construction of a co-expression network. Other data sets (GSE12452 and GSE53819) were used to verify hub genes. The data set GSE102349 was devoted to identify prognostic hub genes by survival analysis. To explored whether prognostic hub genes are related to hypoxia signatures in NPC, correlation analysis was carried out, and followed by functional verification experiments of those genes in vitro. By co-expression network analysis, blue module was regarded as a key module in the benign and malignant group, and IGSF9 of the blue module was identified as a prognostic hub gene. Moreover, IGSF9 is expected to be a innovative hypoxia-related gene in NPC based on the strong associativity between expression of IGSF9 and hypoxia scores of three signatures (99-gene, 26-gene and 15-gene). Further functional studies verified that down-regulated expression of IGSF9 could reduce the proliferation, migration and invasion ability of NPC cells, and hypoxia could induce the expression of IGSF9. IGSF9 was identified to be relevant to prognosis and involved in hypoxia in NPC. IGSF9 might serve as one novel prognostic indicator of NPC in the future.
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