The role of SPI1-TYROBP-FCER1G network in oncogenesis and prognosis of osteosarcoma, and its association with immune infiltration.

The role of SPI1-TYROBP-FCER1G network in oncogenesis and prognosis of osteosarcoma, and its association with immune infiltration.
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SPI1-TYROBP-FCER1G网络在骨肉瘤发生和预后中的作用及其与免疫浸润的关系。

DOI:
10.1186/s12885-022-09216-w
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发表时间:
2022-01-25
期刊:
影响因子:
3.8
通讯作者:
Lu M
Lu M
中科院分区:
医学2区
文献类型:
--
作者:
Li J;Shi H;Yuan Z;Wu Z;Li H;Liu Y;Lu M;Lu M

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骨肉瘤是一种侵袭性的恶性骨肉瘤。一个具有特定功能的致病基因网络在OS的发生和发展中的作用尚不清楚。在这里,我们首先确定了控制和OS样品之间的差异表达基因(DEG),然后定义这些DEG的蛋白质-蛋白质相互作用(PPI)网络中的枢纽基因和顶部簇。通过聚焦于前1个簇中的枢纽基因TYROBP,鉴定了保守的TYROBP共表达网络。然后分析网络对OS总生存期的影响。利用基因本体论(GO)、京都基因和基因组百科全书(KEGG)富集分析和基因集富集分析(GSEA)对网络的功能进行了探索。利用XCell平台和ssGSEA算法对免疫浸润状态进行估计。利用ChEA 3平台、GSEA富集分析和DPS技术预测关键转录因子及其上游信号。我们在OS中鉴定了下调的SPI 1-TYROBP-FCER 1G网络,其在免疫相关功能中显著富集。我们还定义了一个双基因标签(SPI 1/FCER 1G),可以预测OS总生存率较差,下调时免疫浸润减弱。SPI 1-TYROBP-FCER 1G网络可能由转录因子SPI 1启动,并将导致上调CD 86、MHC-II、CCL 4/CXCL 10/CX 3CL 1,从而增加免疫浸润。通过本研究,我们可以更好地探讨OS肿瘤发生和转移的机制,为开发新的治疗方法提供依据。在线版本包含补充材料,可通过10.1186/s12885-022-09216-w获得。
Osteosarcoma is an aggressive malignant bone sarcoma worldwide. A causal gene network with specific functions underlying both the development and progression of OS was still unclear. Here we firstly identified the differentially expressed genes (DEGs) between control and OS samples, and then defined the hub genes and top clusters in the protein–protein interaction (PPI) network of these DEGs. By focusing on the hub gene TYROBP in the top 1 cluster, a conserved TYROBP co-expression network was identified. Then the effect of the network on OS overall survival was analyzed. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and Gene Set Enrichment Analysis (GSEA) were used to explore the functions of the network. XCell platform and ssGSEA algorithm were conducted to estimate the status of immune infiltration. ChEA3 platform, GSEA enrichment analysis, and Drug Pair Seeker (DPS) were used to predict the key transcription factor and its upstream signal. We identified the downregulated SPI1-TYROBP-FCER1G network in OS, which were significantly enriched in immune-related functions. We also defined a two-gene signature (SPI1/FCER1G) that can predict poorer OS overall survival and the attenuated immune infiltration when downregulated. The SPI1-TYROBP-FCER1G network were potentially initiated by transcription factor SPI1 and would lead to the upregulated CD86, MHC-II, CCL4/CXCL10/CX3CL1 and hence increased immune infiltrations. With this study, we could better explore the mechanism of OS oncogenesis and metastasis for developing new therapies. The online version contains supplementary material available at 10.1186/s12885-022-09216-w.
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