Laboratory of Molecular Target Therapy for Cancer, Graduate School for Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Center for Comprehensive Community Medicine, Faculty of Medicine, Saga University, Saga, Japan.
PLoS One. 2020 Feb 26;15(2):e0229577. doi: 10.1371/journal.pone.0229577. eCollection 2020.
MicroRNAs (miRNAs) inhibit protein function by silencing the translation of target mRNAs. However, in primary central nervous system lymphoma (PCNSL), the expression and functions of miRNAs are inadequately known. Here, we examined the expression of 847 miRNAs in 40 PCNSL patients with a microarray and investigated for the miRNA predictors associated with cancer immunity-related genes such as T helper cell type 1/2 (Th-1/Th-2) and regulatory T cell (T-reg) status, and stimulatory and inhibitory checkpoint genes, for prognosis prediction in PCNSL. The aim of this study is to find promising prognosis markers based on the miRNA expression in PCNSL. We detected 334 miRNAs related to 66 cancer immunity-related genes in the microarray profiling. Variable importance measured by the random survival forest analysis and Cox proportional hazards regression model elucidated that 11 miRNAs successfully constitute the survival formulae dividing the Kaplan-Meier curve of the respective PCNSL subgroups. On the other hand, univariate analysis shortlisted 23 miRNAs for overall survival times, with four miRNAs clearly dividing the survival curves-miR-101/548b/554/1202. These miRNAs regulated Th-1/Th-2 status, T-reg cell status, and immune checkpoints. The miRNAs were also associated with gene ontology terms as Ras/MAP-kinase, ubiquitin ligase, PRC2 and acetylation, CDK, and phosphorylation, and several diseases including acquired immunodeficiency syndrome, glioma, and those related to blood and hippocampus with statistical significance. In conclusion, the results demonstrated that the four miRNAs comprising miR-101/548b/554/1202 associated with cancer immunity can be a useful prognostic marker in PCNSL and would help us understand target pathways for PCNSL treatments.
微小 RNA（miRNAs）通过沉默靶 mRNAs 的翻译来抑制蛋白质功能。然而，在原发性中枢神经系统淋巴瘤（PCNSL）中，miRNAs 的表达和功能尚未得到充分了解。在这里，我们使用微阵列检查了 40 名 PCNSL 患者的 847 种 miRNA 的表达情况，并研究了与癌症免疫相关基因（如辅助性 T 细胞 1/2（Th-1/Th-2）和调节性 T 细胞（T-reg）状态以及刺激性和抑制性检查点基因）相关的 miRNA 预测因子，以预测 PCNSL 的预后。本研究的目的是基于 PCNSL 中的 miRNA 表达找到有前途的预后标志物。我们在微阵列分析中检测到 334 种与 66 种癌症免疫相关基因相关的 miRNA。随机生存森林分析和 Cox 比例风险回归模型测量的变量重要性阐明了 11 种 miRNA 成功构成了各自 PCNSL 亚组的生存公式。另一方面，单变量分析筛选出与总生存时间相关的 23 个 miRNA，其中 4 个 miRNA 清楚地划分了生存曲线-miR-101/548b/554/1202。这些 miRNA 调节 Th-1/Th-2 状态、T-reg 细胞状态和免疫检查点。这些 miRNA 还与 Ras/MAP-kinase、泛素连接酶、PRC2 和乙酰化、CDK 和磷酸化以及包括获得性免疫缺陷综合征、神经胶质瘤和与血液和海马体相关的几种疾病的基因本体术语相关，具有统计学意义。总之，结果表明，由 miR-101/548b/554/1202 组成的四种与癌症免疫相关的 miRNA 可以作为 PCNSL 的有用预后标志物，有助于我们了解 PCNSL 治疗的靶途径。
