Malignant Tumor Purity Reveals the Driven and Prognostic Role of CD3E in Low-Grade Glioma Microenvironment.

Xiuqin Lu,Wenhao Xu,Haineng Huang,Yuanyuan Wu,Hailiang Zhang,Huadong Huang,Shuxian Chen,Jian Wang,Jian Wang,Shuxian Chen,Wangrui Liu,Wangrui Liu,Chuanyu Li

doi:10.3389/fonc.2021.676124

Abstract

The tumor microenvironment (TME) contributes to the initiation and progression of many neoplasms. However, the impact of low-grade glioma (LGG) purity on carcinogenesis remains to be elucidated. We selected 509 LGG patients with available genomic and clinical information from the TCGA database. The percentage of tumor infiltrating immune cells and the tumor purity of LGG were evaluated using the ESTIMATE and CIBERSORT algorithms. Stromal-related genes were screened through Cox regression, and protein-protein interaction analyses and survival-related genes were selected in 487 LGG patients from GEO database. Hub genes involved in LGG purity were then identified and functionally annotated using bioinformatics analyses. Prognostic implications were validated in 100 patients from an Asian real-world cohort. Elevated tumor purity burden, immune scores, and stromal scores were significantly associated with poor outcomes and increased grade in LGG patients from the TCGA cohort. In addition, CD3E was selected with the most significant prognostic value (Hazard Ratio=1.552, P<0.001). Differentially expressed genes screened according to CD3E expression were mainly involved in stromal related activities. Additionally, significantly increased CD3E expression was found in 100 LGG samples from the validation cohort compared with adjacent normal brain tissues. High CD3E expression could serve as an independent prognostic indicator for survival of LGG patients and promotes malignant cellular biological behaviors of LGG. In conclusion, tumor purity has a considerable impact on the clinical, genomic, and biological status of LGG. CD3E, the gene for novel membrane immune biomarker deeply affecting tumor purity, may help to evaluate the prognosis and develop individual immunotherapy strategies for LGG patients. Evaluating the ratio of differential tumor purity and CD3E expression levels may provide novel insights into the complex structure of the LGG microenvironment and targeted drug development.

Highlights

The treatment and prognosis of glioma are relatively limited because the understanding of immune gene regulation and carcinogenesis is incomplete [1, 2]
To estimate the proportion of tumor-infiltrating immune cells (TIC) and tumor purity in low-grade glioma (LGG) samples, transcriptome RNA-seq data from 516 patients were downloaded from The Cancer Genome Atlas (TCGA), after which ESTIMATE and CIBERSORT algorithms were performed
Further studies focused on the impact of CD3E on survival, Gene Set Enrichment Analysis (GSEA), and correlation with TICs

Summary

Introduction

The treatment and prognosis of glioma are relatively limited because the understanding of immune gene regulation and carcinogenesis is incomplete [1, 2]. In the United States, the annual incidence of pediatric low-grade glioma (LGG) is 1.3-2.1 cases per 100,000 people, while adult LGG is more common with an estimated 9.1-12.5 cases per 100,000 people [3, 4]. Glioblastoma multiforme (Grade IV) is the second most common primary intracranial tumor, and the most common malignant tumor of the central nervous system. The high recurrence and malignancy rates of LGG are detrimental to patients [7, 8]. Investigating approaches to maintain the quality of life of LGG patients while prolonging their overall survival (OS) has become a common focus for clinicians and researchers [9,10,11,12]

Objectives

Methods

Results

Conclusion