Hypoxia Contributes to Poor Prognosis in Primary IDH-wt GBM by Inducing Tumor Cells MES-Like Transformation Trend and Inhibiting Immune Cells Activity

Zujian Xiong; Hongwei Liu; Chenqi He; Xuejun Li

doi:10.3389/fonc.2021.782043

Hypoxia Contributes to Poor Prognosis in Primary IDH-wt GBM by Inducing Tumor Cells MES-Like Transformation Trend and Inhibiting Immune Cells Activity

Front Oncol. 2021 Dec 8:11:782043. doi: 10.3389/fonc.2021.782043. eCollection 2021.

Authors

Zujian Xiong^{1

2

3}, Hongwei Liu^{1

3}, Chenqi He^{1

3}, Xuejun Li^{1

3}

Affiliations

¹ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
² Xiangya School of Medicine, Central South University, Changsha, China.
³ Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, China.

Abstract

Aims: To reveal the influence of hypoxia on tumor cells and immune cells in primary IDH-wt glioblastoma patients.

Methods: Single-cell RNA-seq data and bulk RNA-seq data were acquired from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, respectively. Hypoxia status and subtypes of tumor cells were identified based on single-sample Gene Set Enrichment Analysis (ssGSEA). Regulon network analysis of different subtypes under different conditions was conducted by SCENIC. Within tumor microenvironment, biological process activity analysis and cell-cell communication network were conducted to uncover the inner links between each cell subtype under different hypoxia status.

Results: Different types of tumor cell in GBM possessed different hypoxia status, and MES-like subtype was under a more severe hypoxia condition than other subtypes. Hypoxia also induced MES-like signature gene expression within each tumor cell, which could stimulate tumor cell proliferation and invasion by regulating cell-cell communication. Additionally, hypoxia inhibited immune cell activity in the tumor microenvironment by inducing macrophage phenotype polarization and upregulating immune-inhibited cell-cell interaction within immune cells. Interactions between tumor cells and immune cells under hypoxia status also promoted tumor progression.

Conclusions: Hypoxia was a poor prognostic marker for primary IDH-wt GBM patients. Meanwhile, it could induce tumor cells' MES-like transformation trend and inhibit antitumor function of immune cells.

Keywords: MES-like transformation; hypoxia; primary IDH-wt GBM; single-cell analysis; tumor immune microenvironment.