Department of Neurosurgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, China.
Department of Surgery of Spine and Spinal Cord, Henan International Joint Laboratory of Intelligentized Orthopedics Innovation and Transformation, Henan Key Laboratory for Intelligent Precision Orthopedics, Microbiome Laboratory, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, China.
Curr Res Transl Med. 2022 Sep;70(4):103345. doi: 10.1016/j.retram.2022.103345. Epub 2022 Apr 26.
The oncogene CLSPN, also known as claspin, has regulatory effects in a variety of tumours; however, it is not clear whether CLSPN is a therapeutic target in low-grade gliomas (LGG). In this study, the prognostic value of CLSPN in LGG and its role as an immunotherapeutic target were evaluated.
Transcriptome and methylation data for thousands of patients with glioma were collected from various databases, including The Cancer Genome Atlas, Chinese Glioma Genome Atlas, and Gene Expression Omnibus. Subsequently, a series of bioinformatics methods were used to evaluate the relationships between CLSPN and prognosis, clinical features, methylation status, immune cells, and molecular signaling pathways in LGG.
CLSPN expression levels were positively correlated with major malignant characteristics of LGG, and low expression of CLSPN was associated with a better prognosis. The methylation sites cg04263115 and cg06100291 negatively regulated the expression of CLSPN, and increased methylation levels at these sites were related to a longer survival time in patients with LGG. CLSPN was positively correlated with tumour-infiltrating immune cells and showed high copy number variation in these cells. There was a positive regulatory relationship between CLSPN expression and programmed death-1 (PD-1) and programmed cell death ligand 1 (PD-L1). A gene set enrichment analysis revealed that CLSPN activates a variety of cancer signaling pathways.
CLSPN was identified as an independent risk factor for LGG with excellent prognostic value.
癌基因 CLSPN，也称为 claspin，在多种肿瘤中具有调节作用；然而，CLSPN 是否是低级别胶质瘤（LGG）的治疗靶点尚不清楚。在这项研究中，评估了 CLSPN 在 LGG 中的预后价值及其作为免疫治疗靶点的作用。
从各种数据库（包括癌症基因组图谱、中国胶质瘤基因组图谱和基因表达综合数据库）收集了数千名胶质瘤患者的转录组和甲基化数据。随后，使用一系列生物信息学方法来评估 CLSPN 与 LGG 中的预后、临床特征、甲基化状态、免疫细胞和分子信号通路之间的关系。
CLSPN 的表达水平与 LGG 的主要恶性特征呈正相关，CLSPN 低表达与预后较好相关。甲基化位点 cg04263115 和 cg06100291 负调控 CLSPN 的表达，这些位点的甲基化水平增加与 LGG 患者的生存时间延长有关。CLSPN 与肿瘤浸润免疫细胞呈正相关，并且在这些细胞中存在高拷贝数变异。CLSPN 表达与程序性死亡受体-1（PD-1）和程序性细胞死亡配体 1（PD-L1）之间存在正调控关系。基因集富集分析表明 CLSPN 激活了多种癌症信号通路。
CLSPN 被鉴定为具有出色预后价值的 LGG 的独立危险因素。
