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

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...

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Main Authors: Xiuqin Lu, Chuanyu Li, Wenhao Xu, Yuanyuan Wu, Jian Wang, Shuxian Chen, Hailiang Zhang, Huadong Huang, Haineng Huang, Wangrui Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-09-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.676124/full
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author Xiuqin Lu
Chuanyu Li
Wenhao Xu
Yuanyuan Wu
Jian Wang
Shuxian Chen
Hailiang Zhang
Huadong Huang
Haineng Huang
Wangrui Liu
Wangrui Liu
author_facet Xiuqin Lu
Chuanyu Li
Wenhao Xu
Yuanyuan Wu
Jian Wang
Shuxian Chen
Hailiang Zhang
Huadong Huang
Haineng Huang
Wangrui Liu
Wangrui Liu
author_sort Xiuqin Lu
collection DOAJ
description 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.
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spelling doaj.art-1de4b80bb7b64d3fbf876840b367eed72022-12-21T21:55:18ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-09-011110.3389/fonc.2021.676124676124Malignant Tumor Purity Reveals the Driven and Prognostic Role of CD3E in Low-Grade Glioma MicroenvironmentXiuqin Lu0Chuanyu Li1Wenhao Xu2Yuanyuan Wu3Jian Wang4Shuxian Chen5Hailiang Zhang6Huadong Huang7Haineng Huang8Wangrui Liu9Wangrui Liu10Department of Nursing and Health Management, Shanghai University of Medicine & Health Sciences, Shanghai, ChinaDepartment of Neurosurgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi, ChinaDepartment of Urology, Fudan University Shanghai Cancer Center, Shanghai Medical University, Fudan University, Shanghai, ChinaDepartment of Gastroenterology, Naval Medical Center of People’s Liberation Army (PLA) of China, Naval Military Medical University, Shanghai, ChinaDepartment of Transplantation, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Oncology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Urology, Fudan University Shanghai Cancer Center, Shanghai Medical University, Fudan University, Shanghai, ChinaDepartment of Neurosurgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi, ChinaDepartment of Neurosurgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi, ChinaDepartment of Nursing and Health Management, Shanghai University of Medicine & Health Sciences, Shanghai, ChinaDepartment of Neurosurgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi, ChinaThe 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.https://www.frontiersin.org/articles/10.3389/fonc.2021.676124/fulltumor microenvironmenttumor purityCD3Elow-grade gliomaprognosisimmune infiltrations
spellingShingle Xiuqin Lu
Chuanyu Li
Wenhao Xu
Yuanyuan Wu
Jian Wang
Shuxian Chen
Hailiang Zhang
Huadong Huang
Haineng Huang
Wangrui Liu
Wangrui Liu
Malignant Tumor Purity Reveals the Driven and Prognostic Role of CD3E in Low-Grade Glioma Microenvironment
Frontiers in Oncology
tumor microenvironment
tumor purity
CD3E
low-grade glioma
prognosis
immune infiltrations
title Malignant Tumor Purity Reveals the Driven and Prognostic Role of CD3E in Low-Grade Glioma Microenvironment
title_full Malignant Tumor Purity Reveals the Driven and Prognostic Role of CD3E in Low-Grade Glioma Microenvironment
title_fullStr Malignant Tumor Purity Reveals the Driven and Prognostic Role of CD3E in Low-Grade Glioma Microenvironment
title_full_unstemmed Malignant Tumor Purity Reveals the Driven and Prognostic Role of CD3E in Low-Grade Glioma Microenvironment
title_short Malignant Tumor Purity Reveals the Driven and Prognostic Role of CD3E in Low-Grade Glioma Microenvironment
title_sort malignant tumor purity reveals the driven and prognostic role of cd3e in low grade glioma microenvironment
topic tumor microenvironment
tumor purity
CD3E
low-grade glioma
prognosis
immune infiltrations
url https://www.frontiersin.org/articles/10.3389/fonc.2021.676124/full
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