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

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.

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“…Additionally, the study found that tumors with a high hub-gene score, low TF and miRNA scores tended to have high tumor purity, low immune and stromal scores, low infiltration levels of activated CD4 and CD8 T cells, central memory CD4 T cell, effector memory CD8 T cell, neutrophil, activated B cell and eosinophil, as well as decreased expressions of exhausted immune markers including CD48, LAG3, CTLA4 and TIGIT. Among the hub genes, PTPRN expression was reported to significantly restraint the infiltrating levels of CD4 T cells, B cells, macrophages, neutrophil, and dendritic cells in low grade glioma ( 46 ). The negative regulation between PTPRN expression and immune response as well as immune cells was also observed in lung adenocarcinoma ( 47 ).…”

“…In hepatocellular carcinoma, patients with a low expression of CDK5R2 in tumor displayed poor overall survival ( 61 ). PTPRN expression, which negatively regulates immune cell infiltration in low grade glioma, is correlated with a favorable prognosis of patients ( 46 ). Another study also reported high immune, stromal and ESTIMATE scores whereas low tumor purity in low-grade-glioma patients with dismal survival ( 62 ).…”