Reciprocal expression of the immune response genes CXCR3 and IFI44L as module hubs are associated with patient survivals in primary central nervous system lymphoma
Reciprocal expression of the immune response genes CXCR3 and IFI44L as module hubs are associated with patient survivals in primary central nervous system lymphoma
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DOI：
10.1007/s10147-022-02285-8
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发表时间：
2023-01-06
影响因子：
3.3
通讯作者：
Yamanaka，Ryuya
中科院分区：
文献类型：
--
作者：
Takashima，Yasuo;Hamano，Momoko;Yamanaka，Ryuya
目的研究原发性中枢神经系统淋巴瘤（PCNSL）中与预后不良相关的肿瘤微环境和免疫反应相关基因相互表达的表达模块。方法通过加权基因共表达网络分析，揭示31份PCNSL样本转录组数据的代表性模块，包括神经发生、免疫反应、抗病毒、微环境、基因表达与翻译、细胞外基质、形态发生和细胞粘附。结果基因表达网络也反映在蛋白-蛋白相互作用网络上。其中，部分枢纽基因在预后良好的PCNSL患者中高表达，如AQP4、SLC1A3、GFAP、CXCL9、CXCL10、GBP2、IFI6、OAS2、IFIT3、DCN、LRP1、lum等，预后良好；stat1、IFITM3、GZMB、ISG15、LY6E、TGFB1、PLAUR、MMP4、FTH1、PLAU、CSF3R、FGR、POSTN、CCR7、TAS1R3、小核糖体亚基基因、胶原型1/3/4/6等预后不良基因。此外，采用Cox比例风险回归模型构建预后预测公式，结果表明IP-10受体基因ecxcr3和I型干扰素诱导蛋白基因eifi44l可以预测PCNSL患者的生存。结论这些结果提示PCNSL肿瘤生长或预后预测可能需要免疫反应和微环境基因的差异表达和平衡，有助于了解PCNSL的肿瘤发生机制和潜在的治疗靶点。
PurposeHere, we investigated expression modules reflecting the reciprocal expression of the cancer microenvironment and immune response-related genes associated with poor prognosis in primary central nervous system lymphoma (PCNSL).MethodsWeighted gene coexpression network analysis revealed representative modules, including neurogenesis, immune response, anti-virus, microenvironment, gene expression and translation, extracellular matrix, morphogenesis, and cell adhesion in the transcriptome data of 31 PCNSL samples.ResultsGene expression networks were also reflected by protein–protein interaction networks. In particular, some of the hub genes were highly expressed in patients with PCNSL with prognoses as follows:AQP4, SLC1A3, GFAP, CXCL9, CXCL10, GBP2, IFI6, OAS2, IFIT3, DCN, LRP1,andLUMwith good prognosis; andSTAT1, IFITM3, GZMB, ISG15, LY6E, TGFB1, PLAUR, MMP4, FTH1, PLAU, CSF3R, FGR, POSTN, CCR7, TAS1R3, small ribosomal subunit genes, and collagen type 1/3/4/6 genes with poor prognosis. Furthermore, prognosis prediction formulae were constructed using the Cox proportional-hazards regression model, which demonstrated that the IP-10 receptor geneCXCR3and type I interferon-induced protein geneIFI44Lcould predict patient survival in PCNSL.ConclusionThese results indicate that the differential expression and balance of immune response and microenvironment genes may be required for PCNSL tumor growth or prognosis prediction, which would help understanding the mechanism of tumorigenesis and potential therapeutic targets in PCNSL.