PTPRN作为低级别胶质瘤的预后生物标志物并与免疫浸润相关。

PTPRN Serves as a Prognostic Biomarker and Correlated with Immune Infiltrates in Low Grade Glioma.

作者信息

Li Peng, Chen Fanfan, Yao Chen, Zhu Kezhou, Zhang Bei, Zheng Zelong

机构信息

VCU Massey Cancer Center, Department of Human and Molecular Genetics, Institute of Molecular Medicine, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.

Neurosurgical Department, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China.

出版信息

Brain Sci. 2022 Jun 10;12(6):763. doi: 10.3390/brainsci12060763.

DOI:10.3390/brainsci12060763

PMID:35741647

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9221056/

Abstract

BACKGROUND

Glioma is one of the most common malignant tumors of the central nervous system. Immune infiltration of tumor microenvironment was associated with overall survival in low grade glioma (LGG). However, effects of Tyrosine phosphatase receptor type N (PTPRN) on the progress of LGG and its correlation with tumor infiltration are unclear.

METHODS

Here, datasets of LGG were from The Cancer Genome Atlas (TCGA) and normal samples were from GTEx dataset. Gepia website and Human Protein Atlas (HPA) Database were used to analyze the mRNA and protein expression of PTPRN. We evaluated the influence of PTPRN on survival of LGG patients. MethSurv was used to explore the expression and prognostic patterns of single CpG methylation of PTPRN gene in LGG. The correlations between the clinical information and PTPRN expression were analyzed using logistic regression and Multivariate Cox regression. We also explored the correlation between PTPRN expression and cancer immune infiltration by TIMER. Gene set enrichment analysis (GSEA) was formed using TCGA RNA-seq datasets.

RESULTS

PTPRN mRNA and protein expression decreased in LGG compared to normal brain tissue in TCGA and HPA database. Kaplan-Meier analysis showed that the high expression level of PTPRN correlated with a good overall survival (OS) of patients with LGG. The Multivariate Cox analysis demonstrated that PTPRN expression and other clinical-pathological factors (age, WHO grade, IDH status, and primary therapy outcome) significantly correlated with OS of LGG patients. The DNA methylation pattern of PTPRN with significant prognostic value were confirmed, including cg00672332, cg06971096, cg01382864, cg03970036, cg10140638, cg16166796, cg03545227, and cg25569248. Interestingly, PTPRN expression level significantly negatively correlated with infiltrating level of B cell, CD4+ T cells, Macrophages, Neutrophils, and DCs in LGG. Finally, GSEA showed that signaling pathways, mainly associated with tumor microenvironment and immune cells, were significantly enriched in PTPRN high expression.

CONCLUSION

PTPRN is a potential biomarker and correlates with tumor immune infiltration in LGG.

摘要

背景

胶质瘤是中枢神经系统最常见的恶性肿瘤之一。肿瘤微环境的免疫浸润与低级别胶质瘤（LGG）的总生存期相关。然而，N型酪氨酸磷酸酶受体（PTPRN）对LGG进展的影响及其与肿瘤浸润的相关性尚不清楚。

方法

本研究中，LGG数据集来自癌症基因组图谱（TCGA），正常样本来自基因型组织表达（GTEx）数据集。利用Gepia网站和人类蛋白质图谱（HPA）数据库分析PTPRN的mRNA和蛋白质表达。我们评估了PTPRN对LGG患者生存的影响。使用甲基化生存分析（MethSurv）探索LGG中PTPRN基因单个CpG甲基化的表达和预后模式。采用逻辑回归和多变量Cox回归分析临床信息与PTPRN表达之间的相关性。我们还通过肿瘤免疫估计资源（TIMER）探索PTPRN表达与癌症免疫浸润之间的相关性。利用TCGA RNA测序数据集进行基因集富集分析（GSEA）。

结果

在TCGA和HPA数据库中，与正常脑组织相比，LGG中PTPRN的mRNA和蛋白质表达降低。Kaplan-Meier分析显示，PTPRN高表达与LGG患者良好的总生存期（OS）相关。多变量Cox分析表明，PTPRN表达和其他临床病理因素（年龄、世界卫生组织分级、异柠檬酸脱氢酶状态和初始治疗结果）与LGG患者的OS显著相关。证实了具有显著预后价值的PTPRN的DNA甲基化模式，包括cg00672332、cg06971096、cg01382864、cg03970036、cg10140638、cg16166796、cg03545227和cg25569248。有趣的是，LGG中PTPRN表达水平与B细胞、CD4+T细胞、巨噬细胞、中性粒细胞和树突状细胞的浸润水平显著负相关。最后，GSEA显示，主要与肿瘤微环境和免疫细胞相关的信号通路在PTPRN高表达中显著富集。