Immune Cluster and PPI Network Analyses Identified CXCR3 as a Key Node of Immunoregulation in Head and Neck Cancer
The tumor microenvironment (TME) is significantly associated with clinical outcomes and therapeutic efficacy. However, the landscape of the head and neck cancer (HNC) microenvironment is not fully understood. Therefore, we divided HNCs into three classes according to differences in the TME to determ...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.564306/full |
| _version_ | 1818610801498390528 |
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| author | Ping Wang Yanli Wang Yuanjun Jiang Minghong Li Guang Li Qiao Qiao |
| author_facet | Ping Wang Yanli Wang Yuanjun Jiang Minghong Li Guang Li Qiao Qiao |
| author_sort | Ping Wang |
| collection | DOAJ |
| description | The tumor microenvironment (TME) is significantly associated with clinical outcomes and therapeutic efficacy. However, the landscape of the head and neck cancer (HNC) microenvironment is not fully understood. Therefore, we divided HNCs into three classes according to differences in the TME to determine effective personalized treatments. We explored the immune landscape of head and neck cancer by analysing the gene expression profile of 501 cases from the Cancer Genome Atlas (TCGA) data portal and validated our findings in 270 cases from the Gene Expression Omnibus (GEO) database. The levels of immune components in the tumor microenvironment were evaluated via single-sample gene set enrichment (ssGSEA) analysis. The HNCs were clustered into an Immunity-H group, Immunity-M group and Immunity-L group according to 40 immune components in the tumor microenvironment. DNA damage and HLA genes play an important role in immune regulation. The patients in the Immunity-H group had a favourable survival compared with patients in the Immunity-M group and the Immunity-L group. The patients in the Immunity-H group and Immunity-M group could benefit from radiotherapy. In addition, the Immunity-L group showed the lowest immunophenoscore and had poor response to anti-PD-1 treatment. CXCR3 was demonstrated to be downregulated in the Immunity-L group, which was related to shorter OS in the TCGA and GEO databases, suggesting CXCR3 as a potential therapeutic target. Taken together, our findings proposed three new microenvironment-related phenotypes of HNCs and suggested that CXCR3 played a major role in immune regulation and could be a novel therapeutic target, providing a reference for clinical decisions and research directions in the future. |
| first_indexed | 2024-12-16T15:20:12Z |
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| id | doaj.art-2853f3fa8a874ea995168b064f1c4ff4 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-16T15:20:12Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-2853f3fa8a874ea995168b064f1c4ff42022-12-21T22:26:39ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-01-011010.3389/fonc.2020.564306564306Immune Cluster and PPI Network Analyses Identified CXCR3 as a Key Node of Immunoregulation in Head and Neck CancerPing Wang0Yanli Wang1Yuanjun Jiang2Minghong Li3Guang Li4Qiao Qiao5Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, ChinaDepartment of Radiation Oncology, The First Hospital of China Medical University, Shenyang, ChinaDepartment of Urology, The First Hospital of China Medical University, Shenyang, ChinaDepartment of Otolaryngology, The First Hospital of China Medical University, Shenyang, ChinaDepartment of Radiation Oncology, The First Hospital of China Medical University, Shenyang, ChinaDepartment of Radiation Oncology, The First Hospital of China Medical University, Shenyang, ChinaThe tumor microenvironment (TME) is significantly associated with clinical outcomes and therapeutic efficacy. However, the landscape of the head and neck cancer (HNC) microenvironment is not fully understood. Therefore, we divided HNCs into three classes according to differences in the TME to determine effective personalized treatments. We explored the immune landscape of head and neck cancer by analysing the gene expression profile of 501 cases from the Cancer Genome Atlas (TCGA) data portal and validated our findings in 270 cases from the Gene Expression Omnibus (GEO) database. The levels of immune components in the tumor microenvironment were evaluated via single-sample gene set enrichment (ssGSEA) analysis. The HNCs were clustered into an Immunity-H group, Immunity-M group and Immunity-L group according to 40 immune components in the tumor microenvironment. DNA damage and HLA genes play an important role in immune regulation. The patients in the Immunity-H group had a favourable survival compared with patients in the Immunity-M group and the Immunity-L group. The patients in the Immunity-H group and Immunity-M group could benefit from radiotherapy. In addition, the Immunity-L group showed the lowest immunophenoscore and had poor response to anti-PD-1 treatment. CXCR3 was demonstrated to be downregulated in the Immunity-L group, which was related to shorter OS in the TCGA and GEO databases, suggesting CXCR3 as a potential therapeutic target. Taken together, our findings proposed three new microenvironment-related phenotypes of HNCs and suggested that CXCR3 played a major role in immune regulation and could be a novel therapeutic target, providing a reference for clinical decisions and research directions in the future.https://www.frontiersin.org/articles/10.3389/fonc.2020.564306/fullhead and neck cancertumor microenvironmentsingle-sample gene set enrichment analysisthe Cancer Genome Atlasprognosistreatment |
| spellingShingle | Ping Wang Yanli Wang Yuanjun Jiang Minghong Li Guang Li Qiao Qiao Immune Cluster and PPI Network Analyses Identified CXCR3 as a Key Node of Immunoregulation in Head and Neck Cancer Frontiers in Oncology head and neck cancer tumor microenvironment single-sample gene set enrichment analysis the Cancer Genome Atlas prognosis treatment |
| title | Immune Cluster and PPI Network Analyses Identified CXCR3 as a Key Node of Immunoregulation in Head and Neck Cancer |
| title_full | Immune Cluster and PPI Network Analyses Identified CXCR3 as a Key Node of Immunoregulation in Head and Neck Cancer |
| title_fullStr | Immune Cluster and PPI Network Analyses Identified CXCR3 as a Key Node of Immunoregulation in Head and Neck Cancer |
| title_full_unstemmed | Immune Cluster and PPI Network Analyses Identified CXCR3 as a Key Node of Immunoregulation in Head and Neck Cancer |
| title_short | Immune Cluster and PPI Network Analyses Identified CXCR3 as a Key Node of Immunoregulation in Head and Neck Cancer |
| title_sort | immune cluster and ppi network analyses identified cxcr3 as a key node of immunoregulation in head and neck cancer |
| topic | head and neck cancer tumor microenvironment single-sample gene set enrichment analysis the Cancer Genome Atlas prognosis treatment |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2020.564306/full |
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