Background Host response diffuse large B-cell lymphoma (HR DLBCL) shares features of histologically defined T-cell/histiocyte-rich B-cell lymphoma, including fewer genetic abnormalities, frequent splenic and bone marrow involvement, and younger age at presentation. HR DLBCL is inherently less responsive to the standard treatment for DLBCL. Moreover, the mechanism of infiltration of HR DLBCL with preexisting abundant T-cells and dendritic cells is unknown, and their associated underlying immune responses incompletely defined. Here, hub genes and pathogenesis associated with HR DLBCL were explored to reveal molecular mechanisms and treatment targets. Methods Differentially expressed genes were identified in three datasets (GSE25638, GSE44337, GSE56315). The expression profile of the genes in the GSE53786 dataset was used to constructed a co-expression network. Protein-protein interactions analysis in the modules of interest identified candidate hub genes. Then screening of real hub genes was carried out by survival analysis within the GSE53786 and GSE10846 datasets. Expression of hub genes was validated in the Gene expression profiling interactive analysis, Oncomine databases and human tissue specimens. Functional enrichment analysis and Gene set enrichment analysis were utilized to investigate the potential mechanisms. Tumor Immune Estimation Resource and The Cancer Genome Atlas were used to mine the association of the hub gene with tumor immunity, potential upstream regulators were predicted using bioinformatics tools. Results A total of 274 common differentially expressed genes were identified. Within the key module, we identified CXCL10 as a real hub gene. The validation of upregulated expression level of CXCL10 was consistent with our study. CXCL10 might have a regulatory effect on tumor immunity. The predicted miRNA (hsa-mir-6849-3p) and transcription factor (IRF9) might regulate gene expression in the hub module.

中文翻译：

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通过综合生物信息学分析鉴定与以宿主反应为特征的弥漫性大 B 细胞淋巴瘤亚型发病机制相关的枢纽基因

背景 宿主反应弥漫性大 B 细胞淋巴瘤 (HR DLBCL) 具有组织学定义的 T 细胞/富含组织细胞的 B 细胞淋巴瘤的共同特征，包括较少的遗传异常、频繁的脾脏和骨髓受累以及发病年龄较小。HR DLBCL 本质上对 DLBCL 的标准治疗反应较差。此外，HR DLBCL 与预先存在的丰富 T 细胞和树突状细胞浸润的机制尚不清楚，其相关的潜在免疫反应也未完全确定。在这里，探索与 HR DLBCL 相关的中心基因和发病机制，以揭示分子机制和治疗靶点。方法在三个数据集（GSE25638、GSE44337、GSE56315）中鉴定出差异表达的基因。GSE53786数据集中基因的表达谱用于构建共表达网络。感兴趣的模块中的蛋白质-蛋白质相互作用分析确定了候选中枢基因。然后通过 GSE53786 和 GSE10846 数据集中的生存分析对真正的中枢基因进行筛选。枢纽基因的表达在基因表达谱交互分析、Oncomine 数据库和人体组织样本中得到验证。功能富集分析和基因集富集分析被用来研究潜在的机制。肿瘤免疫估计资源和癌症基因组图谱用于挖掘中心基因与肿瘤免疫的关联，使用生物信息学工具预测潜在的上游调节因子。结果共鉴定出274个常见的差异表达基因。在关键模块中，我们将 CXCL10 确定为真正的中心基因。CXCL10 表达水平上调的验证与我们的研究一致。CXCL10可能对肿瘤免疫有调节作用。预测的 miRNA (hsa-mir-6849-3p) 和转录因子 (IRF9) 可能调节中枢模块中的基因表达。