Immune-Related Gene SERPINE1 Is a Novel Biomarker for Diffuse Lower-Grade Gliomas via Large-Scale Analysis

Abstract

BackgroundGlioma is one of the highly fatal primary tumors in the central nervous system. As a major component of tumor microenvironment (TME), immune cell has been proved to play a critical role in the progression and prognosis of the diffuse lower-grade gliomas (LGGs). This study aims to screen the key immune-related factors of LGGs by investigating the TCGA database.MethodsThe RNA-sequencing data of 508 LGG patients were downloaded in the TCGA database. ESTIMATE algorithm was utilized to calculate the stromal, immune, and ESTIMATE scores, based on which, the differentially expressed genes (DEGs) were analyzed by using “limma” package. Cox regression analysis and the cytoHubba plugin of Cytoscape software were subsequently applied to screen the survival-related genes and hub genes, the intersection of which led to the identification of SERPINE1 that played key roles in the LGGs. The expression patterns, clinical features, and regulatory mechanisms of SERPINE1 in the LGGs were further analyzed by data mining of the TCGA database. What’s more, the above analyses of SERPINE1 were further validated in the LGG cohort from the CGGA database.ResultWe found that stromal and immune cell infiltrations were strongly related to the prognosis and malignancy of the LGGs. A total of 54 survival-related genes and 46 hub genes were screened out in the DEGs, within which SERPINE1 was identified to be significantly overexpressed in the LGG samples compared with the normal tissues. Moreover, the upregulation of SERPINE1 was more pronounced in the gliomas of WHO grade III and IDH wild type, and its expression was correlated with poor prognosis in the LGG patients. The independent prognostic value of SERPINE1 in the LGG patients was also confirmed by Cox regression analysis. In terms of the functions of SERPINE1, the results of enrichment analysis indicated that SERPINE1 was mainly enriched in the immune‐related biological processes and signaling pathways. Furthermore, it was closely associated with infiltrations of immune cells in the LGG microenvironment and acted synergistically with PD1, PD-L1, PD-L2.ConclusionThese findings proved that SERPINE1 could serve as a prognostic biomarker and potential immunotherapy target of LGGs.

SERPINE1 Overexpression Promotes Malignant Progression and Poor Prognosis of Gastric Cancer

“…Previous studies showed that SERPINE1 had focused on its effect on thrombosis in humans [ 10 ]. Using high-throughput sequencing technology, SERPINE1 was found to be significantly overexpressed in a variety of tumor tissues [ 11 ]. It has been reported that SERPINE1 can be used as a proliferation regulator of glioblastoma, and its high expression can promote the proliferation and invasion of glioma cells [ 12 ].…”

CD86 Molecule Might Be a Novel Immune-Related Prognostic Biomarker for Patients With Bladder Cancer by Bioinformatics and Experimental Assays

“…After conducting WGCNA, a total of 45 potential hub genes were identified. Lu et al used CytoHubba MCC method in their study to screen out hub genes, whereas Huang et al identified serpin family E member 1 (SERPINE1) as a novel biomarker for diffuse lower-grade gliomas via CytoHubba stress algorithm and CytoHubba betweenness algorithm (49,50). Considering that all these algorithms were effective methods to screen out hub genes, we screened out three hub genes among the 45 genes by using all the algorithms in the present study to make our results credible.…”

The N6-Methylandenosine-Related Gene BIRC5 as a Prognostic Biomarker Correlated With Cell Migration and Immune Cell Infiltrates in Low Grade Glioma

“…Glioma is a highly fatal primary tumor of the central nervous system. Despite diverse available therapeutic strategies, including surgery, chemotherapy, and immunotherapy, the median survival of people with glioma—which has barely improved since its recognition as a separate cancer type—remains only approximately 14 months ( Huang et al, 2021 ). Therefore, more sensitive and specific diagnostic biomarkers and potential therapeutic targets for glioma patients are of no delay.…”