首都医科大学学报 ›› 2023, Vol. 44 ›› Issue (5): 724-732.doi: 10.3969/j.issn.1006-7795.2023.05.004

• 恶性肿瘤诊治进展 • 上一篇    下一篇

海马钙素类1在原发性中枢神经系统淋巴瘤中表达和临床预后的生物信息学分析

于建宇,郑义,李文斌*   

  1. 首都医科大学附属北京天坛医院神经肿瘤综合治疗病区,北京 100071
  • 收稿日期:2023-07-18 出版日期:2023-10-20 发布日期:2023-10-26
  • 通讯作者: 李文斌 E-mail:liwenbin@ccmu.edu.cn
  • 基金资助:
    国家自然科学基金项目(81972338), 2020北京市临床重点专科项目,首都医科大学附属北京天坛医院人才引进项目(RCYJ-2020-2025-LWB)

Bioinformatics analysis of hippocalcin like 1 expression and clinical prognosis in primary central nervous system lymphoma

Yu Jianyu, Zheng Yi, Li Wenbin*   

  1. Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100071, China
  • Received:2023-07-18 Online:2023-10-20 Published:2023-10-26
  • Supported by:
    This study was supported by National Natural Science Foundation of China(81972338), Clinical Major Specialty Project of Beijing in 2020,Beijing Tiantan Hospital Talent Recruitment(RCYJ-2020-2025-LWB).

摘要: 目的  基于生物信息学分析原发性中枢神经系统淋巴瘤(primary central nervous system lymphoma,PCNSL)中海马钙素类1(hippocalcin like 1,HPCAL1)的表达水平及临床意义,进而推断HPCAL1在PCNSL中的作用。方法  通过基因表达数据库(Gene Expression Omnibus database,GEO)GSE25297数据集下载7例PCNSL组织和7例正常脑组织的表达数据和临床信息,绘制HPCAL1表达水平诊断价值的受试者工作特征曲线(receiver operating characteristic curve, ROC);从GSE34771数据集中下载34例PCNSL患者的表达数据及临床信息,并以HPCAL1表达量的中位值分为高低表达两组,绘制高低表达组的生存曲线、HPCAL1表达量及临床信息的多因素预后分析、高低表达两组差异表达基因的火山图以及热图、差异表达基因的基因本体(Gene Ontology,GO)分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析以及前20个上下调差异基因的蛋白互作网络(protein-protein interaction networks,PPI)分析。结果  HPCAL1的表达量是独立预后因素且可以作为是否患病的依据;与HPCAL1低表达组相比,高表达组的总生存期更长;通过GO分析可知,差异基因主要集中于维持细胞稳态、促进细胞分化、抑制细胞无限增殖和迁移、抑制神经突触的传递等分子功能上;通过KEGG通路分析可知,差异基因主要集中于细胞因子与细胞因子受体互动、溶酶体、吞噬体、炎症相关等免疫相关通路和Rap1信号通路、细胞外基质受体相互作用、代谢通路等功能相关通路上。结论  与HPCAL1低表达组相比,高表达组预后较好。可以根据HPCAL1的表达水平,对PCNSL患者进行干预,有必要将HPCAL1基因作为PCNSL的候选生物标志物。

关键词: 海马钙素类1, 原发性中枢神经系统淋巴瘤, 生物标志物

Abstract: Objective  To infer the role of HPCAL1 in primary central nervous system lymphoma (PCNSL) based on bioinformatics analysis of the expression level and clinical significance of hippocalcin like 1 (HPCAL1) in PCNSL. Methods  The expression data and clinical information of 7 PCNSL tissues and 7 normal brain tissues were downloaded from the GSE25297 dataset in the Gene Expression Omnibus (GEO) database to plot the receiver operating characteristic  (ROC) curve of diagnostic value of HPCAL1 expression level. The expression data and clinical information of 34 PCNSL patients were downloaded from the GSE34771 dataset, and divided into two groups with high and low expression according to the median HPCAL1 expression level, and the survival curves of the high and low expression groups, the multivariate prognostic analysis of HPCAL1 expression and clinical information, the volcano map and heat map of differentially expressed genes in the high-low expression group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differentially expressed genes, and the protein interaction network (PPI) analysis of the first 20 up-regulated and down-regulated differentially expressed genes were mapped. Results  The expression of HPCAL1 is an independent prognostic factor and can be used as a basis for whether there is a disease or not. Compared with the HPCAL1 low-expression group, the high-expression group showed a longer overall survival. Through GO analysis, differential genes mainly focus on molecular functions such as maintaining cell homeostasis, promoting cell differentiation, inhibiting cell infinite proliferation and migration, and inhibiting transmission of nerve synapses. According to KEGG pathway analysis, differential genes were mainly concentrated in immune-related pathways such as cytokine-cytokine receptor interaction, lysosome, phagosome, and inflammation, and functional pathways such as Rap1 signaling pathway, extracellular matrix receptor interaction, and metabolic pathway. Conclusions  Compared with the HPCAL1 low-expression group, the high-expression group showed a better prognosis. According to the expression level of HPCAL1, PCNSL patients can be intervened, and it is necessary to use HPCAL1 gene as a candidate biomarker for PCNSL. 

Key words: hippocalcin like 1, primary central nervous system lymphoma, biomarker

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