Hypoxia Contributes to Poor Prognosis in Primary IDH-wt GBM by Inducing Tumor Cells MES-Like Transformation Trend and Inhibiting Immune Cells Activity
AimsTo reveal the influence of hypoxia on tumor cells and immune cells in primary IDH-wt glioblastoma patients.MethodsSingle-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 sub...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.782043/full |
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| author | Zujian Xiong Zujian Xiong Zujian Xiong Hongwei Liu Hongwei Liu Chenqi He Chenqi He Xuejun Li Xuejun Li |
| author_facet | Zujian Xiong Zujian Xiong Zujian Xiong Hongwei Liu Hongwei Liu Chenqi He Chenqi He Xuejun Li Xuejun Li |
| author_sort | Zujian Xiong |
| collection | DOAJ |
| description | AimsTo reveal the influence of hypoxia on tumor cells and immune cells in primary IDH-wt glioblastoma patients.MethodsSingle-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.ResultsDifferent 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.ConclusionsHypoxia 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. |
| first_indexed | 2024-12-14T07:13:01Z |
| format | Article |
| id | doaj.art-2b2198f167d7487fa3988839b459ef03 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-14T07:13:01Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-2b2198f167d7487fa3988839b459ef032022-12-21T23:11:46ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-12-011110.3389/fonc.2021.782043782043Hypoxia Contributes to Poor Prognosis in Primary IDH-wt GBM by Inducing Tumor Cells MES-Like Transformation Trend and Inhibiting Immune Cells ActivityZujian Xiong0Zujian Xiong1Zujian Xiong2Hongwei Liu3Hongwei Liu4Chenqi He5Chenqi He6Xuejun Li7Xuejun Li8Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, ChinaXiangya School of Medicine, Central South University, Changsha, ChinaHunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, ChinaHunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, ChinaHunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, ChinaHunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Xiangya Hospital, Central South University, Changsha, ChinaAimsTo reveal the influence of hypoxia on tumor cells and immune cells in primary IDH-wt glioblastoma patients.MethodsSingle-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.ResultsDifferent 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.ConclusionsHypoxia 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.https://www.frontiersin.org/articles/10.3389/fonc.2021.782043/fullprimary IDH-wt GBMsingle-cell analysishypoxiaMES-like transformationtumor immune microenvironment |
| spellingShingle | Zujian Xiong Zujian Xiong Zujian Xiong Hongwei Liu Hongwei Liu Chenqi He Chenqi He Xuejun Li Xuejun Li Hypoxia Contributes to Poor Prognosis in Primary IDH-wt GBM by Inducing Tumor Cells MES-Like Transformation Trend and Inhibiting Immune Cells Activity Frontiers in Oncology primary IDH-wt GBM single-cell analysis hypoxia MES-like transformation tumor immune microenvironment |
| title | Hypoxia Contributes to Poor Prognosis in Primary IDH-wt GBM by Inducing Tumor Cells MES-Like Transformation Trend and Inhibiting Immune Cells Activity |
| title_full | Hypoxia Contributes to Poor Prognosis in Primary IDH-wt GBM by Inducing Tumor Cells MES-Like Transformation Trend and Inhibiting Immune Cells Activity |
| title_fullStr | Hypoxia Contributes to Poor Prognosis in Primary IDH-wt GBM by Inducing Tumor Cells MES-Like Transformation Trend and Inhibiting Immune Cells Activity |
| title_full_unstemmed | Hypoxia Contributes to Poor Prognosis in Primary IDH-wt GBM by Inducing Tumor Cells MES-Like Transformation Trend and Inhibiting Immune Cells Activity |
| title_short | Hypoxia Contributes to Poor Prognosis in Primary IDH-wt GBM by Inducing Tumor Cells MES-Like Transformation Trend and Inhibiting Immune Cells Activity |
| title_sort | hypoxia contributes to poor prognosis in primary idh wt gbm by inducing tumor cells mes like transformation trend and inhibiting immune cells activity |
| topic | primary IDH-wt GBM single-cell analysis hypoxia MES-like transformation tumor immune microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.782043/full |
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