Zhang Linyun, Sun Fei, Lu Xiaona, Wang Xiaotong, Wang Jie, Li Jun, Xu Yingsong, Kou Daqing, Lv Hongtao, Don Bin
Department of Neurosurgery, First Affiliated Hospital of Dalian Medical University, Dalian, China.
Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
Front Genet. 2022 Aug 17;13:921823. doi: 10.3389/fgene.2022.921823. eCollection 2022.
Primary central nervous system lymphoma (PCNSL) is a rare B-cell lymphoma of central nervous system, which is often found in immunocompromised patients. The common clinical treatment of PCNSL is methotrexate (MTX) and whole brain radiation therapy. With the development of tumour immunology research, the tumour microenvironment of PCNSL is characterised by abnormal expression of different immune signature molecules and patients with PCNSL may benefit from tumour immunotherapy. In our research, RNA-seq data from 82 PCNSL patients were collated by mining the microarray data from the GEO database. All samples were classified into three types related to tumour immune response by the Cibersort algorithm and consistent clustering. Differential analysis of genes was used to uncover 2 sets of differential genes associated with tumour immunity. The ICI scores of each sample were obtained by PCA algorithm, and the relationship between ICI scores and immune checkpoint expression, immunotherapy and drug sensitivity was investigated. Genes associated with ICI scores and their functional characteristics were investigated by WGCNA analysis and PPI analysis, based on the ICI scores of each sample. The tumour microenvironment in PCNSL has a greater relationship with the tumour immune response. ICI scores obtained from 375 differential genes were associated with multiple immune responses in PCNSL. PCNSL patients with higher ICI scores had a better tumour microenvironment and were sensitive to immunotherapy and some small molecule drug. This study also identified 64 genes associated with ICI scores, which may serve as important therapeutic and prognostic targets for PCNSL. The presence of multiple immunosuppressive responses in the tumour microenvironment of PCNSL which suggested that improving the immune function of PCNSL patients through immunotherapy and targeted therapies can be an effective treatment for PCNSL. And the ICI score and associated genes may also provide a better predictor of the clinical use of immunotherapy.
原发性中枢神经系统淋巴瘤（PCNSL）是一种罕见的中枢神经系统B细胞淋巴瘤，常见于免疫功能低下的患者。PCNSL的常见临床治疗方法是甲氨蝶呤（MTX）和全脑放射治疗。随着肿瘤免疫学研究的发展，PCNSL的肿瘤微环境具有不同免疫特征分子的异常表达，PCNSL患者可能从肿瘤免疫治疗中获益。在我们的研究中，通过挖掘GEO数据库中的微阵列数据，整理了82例PCNSL患者的RNA测序数据。通过Cibersort算法和一致性聚类将所有样本分为与肿瘤免疫反应相关的三种类型。基因差异分析用于发现两组与肿瘤免疫相关的差异基因。通过主成分分析（PCA）算法获得每个样本的免疫检查点抑制剂（ICI）评分，并研究ICI评分与免疫检查点表达、免疫治疗和药物敏感性之间的关系。基于每个样本的ICI评分，通过加权基因共表达网络分析（WGCNA）和蛋白质-蛋白质相互作用（PPI）分析研究与ICI评分相关的基因及其功能特征。PCNSL中的肿瘤微环境与肿瘤免疫反应有更大的关系。从375个差异基因获得的ICI评分与PCNSL中的多种免疫反应相关。ICI评分较高的PCNSL患者具有较好的肿瘤微环境，对免疫治疗和一些小分子药物敏感。本研究还鉴定了64个与ICI评分相关的基因，这些基因可能作为PCNSL重要的治疗和预后靶点。PCNSL肿瘤微环境中存在多种免疫抑制反应，这表明通过免疫治疗和靶向治疗改善PCNSL患者的免疫功能可能是PCNSL的有效治疗方法。并且ICI评分和相关基因也可能为免疫治疗的临床应用提供更好的预测指标。
