TOX correlates with prognosis, immune infiltration, and T cells exhaustion in lung adenocarcinoma
Abstract Background Thymocyte selection‐associated high mobility group box (TOX) plays a crucial role on the development of innate immunity and tumor microenvironment. This study aims to explore the prognostic potential of TOX and comprehensively analyze the correlations between TOX, immune infiltra...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-09-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.3324 |
| _version_ | 1818281301130608640 |
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| author | Longbin Guo Xuanzi Li Rongping Liu Yulei Chen Chen Ren Shasha Du |
| author_facet | Longbin Guo Xuanzi Li Rongping Liu Yulei Chen Chen Ren Shasha Du |
| author_sort | Longbin Guo |
| collection | DOAJ |
| description | Abstract Background Thymocyte selection‐associated high mobility group box (TOX) plays a crucial role on the development of innate immunity and tumor microenvironment. This study aims to explore the prognostic potential of TOX and comprehensively analyze the correlations between TOX, immune infiltration, and T cells function in diverse cancers particularly lung adenocarcinoma (LUAD). Methods TIMER was used to analyze TOX expression in different cancers. Potential prognostic value of TOX was evaluated by the PrognoScan, Kaplan‐Meier Plotter, and GEPIA2. The relationships between TOX, immune infiltration, and related gene marker sets were analyzed by TIMER and GEPIA2. Single‐cell RNA‐seq for T cells in LUAD was analyzed to further investigate the correlations between TOX expression and different T cells populations. Results TOX downregulates in most of the cancer types and correlates with poor prognosis in LUAD. TOX shows significant impacts on survival of LUAD with early stage, ever‐smoking, or low‐TMB status. Increased TOX expression positively correlates with high immune infiltration levels in most of the immune cells and functional T cells including exhausted T cells. Moreover, multiple key genes of exhausted T cells comprising PD‐1, TIM‐3, TIGHT, and CXCL13 have remarkable interaction with TOX. Specifically, TOX is observed with high enrichment in exhausted CD4+ and CD8+ T cells populations in single‐cell RNA‐seq analysis for LUAD. Conclusion TOX is a prognosis‐related biomarker for multiple cancer types especially LUAD. Increased TOX expression significantly increase immune infiltration levels in most of the immune cells comprising CD8+ T cells, CD4+ T cells, mast cells, and functional T cells. Moreover, we verified that TOX highly correlates with exhausted T cells and is probable a critical regulator promoted T cells exhaustion in LUAD. Detection of TOX expression could help to predict prognosis and regulating TOX expression in exhausted T cells may offer a novel strategy in maximizing immunotherapy efficacy for LUAD. |
| first_indexed | 2024-12-13T00:02:56Z |
| format | Article |
| id | doaj.art-23ca59a7145f4ddbb6b1a6e66f93bc07 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-13T00:02:56Z |
| publishDate | 2020-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-23ca59a7145f4ddbb6b1a6e66f93bc072022-12-22T00:06:21ZengWileyCancer Medicine2045-76342020-09-019186694670910.1002/cam4.3324TOX correlates with prognosis, immune infiltration, and T cells exhaustion in lung adenocarcinomaLongbin Guo0Xuanzi Li1Rongping Liu2Yulei Chen3Chen Ren4Shasha Du5Department of Radiation Oncology Nanfang HospitalSouthern Medical University Guangzhou ChinaDepartment of Radiation Oncology Nanfang HospitalSouthern Medical University Guangzhou ChinaDepartment of Radiation Oncology Nanfang HospitalSouthern Medical University Guangzhou ChinaDepartment of Radiation Oncology Nanfang HospitalSouthern Medical University Guangzhou ChinaDepartment of Radiation Oncology Nanfang HospitalSouthern Medical University Guangzhou ChinaDepartment of Radiation Oncology Nanfang HospitalSouthern Medical University Guangzhou ChinaAbstract Background Thymocyte selection‐associated high mobility group box (TOX) plays a crucial role on the development of innate immunity and tumor microenvironment. This study aims to explore the prognostic potential of TOX and comprehensively analyze the correlations between TOX, immune infiltration, and T cells function in diverse cancers particularly lung adenocarcinoma (LUAD). Methods TIMER was used to analyze TOX expression in different cancers. Potential prognostic value of TOX was evaluated by the PrognoScan, Kaplan‐Meier Plotter, and GEPIA2. The relationships between TOX, immune infiltration, and related gene marker sets were analyzed by TIMER and GEPIA2. Single‐cell RNA‐seq for T cells in LUAD was analyzed to further investigate the correlations between TOX expression and different T cells populations. Results TOX downregulates in most of the cancer types and correlates with poor prognosis in LUAD. TOX shows significant impacts on survival of LUAD with early stage, ever‐smoking, or low‐TMB status. Increased TOX expression positively correlates with high immune infiltration levels in most of the immune cells and functional T cells including exhausted T cells. Moreover, multiple key genes of exhausted T cells comprising PD‐1, TIM‐3, TIGHT, and CXCL13 have remarkable interaction with TOX. Specifically, TOX is observed with high enrichment in exhausted CD4+ and CD8+ T cells populations in single‐cell RNA‐seq analysis for LUAD. Conclusion TOX is a prognosis‐related biomarker for multiple cancer types especially LUAD. Increased TOX expression significantly increase immune infiltration levels in most of the immune cells comprising CD8+ T cells, CD4+ T cells, mast cells, and functional T cells. Moreover, we verified that TOX highly correlates with exhausted T cells and is probable a critical regulator promoted T cells exhaustion in LUAD. Detection of TOX expression could help to predict prognosis and regulating TOX expression in exhausted T cells may offer a novel strategy in maximizing immunotherapy efficacy for LUAD.https://doi.org/10.1002/cam4.3324immune infiltrationimmunotherapylung adenocarcinomaprognosisT cells exhaustionTOX |
| spellingShingle | Longbin Guo Xuanzi Li Rongping Liu Yulei Chen Chen Ren Shasha Du TOX correlates with prognosis, immune infiltration, and T cells exhaustion in lung adenocarcinoma Cancer Medicine immune infiltration immunotherapy lung adenocarcinoma prognosis T cells exhaustion TOX |
| title | TOX correlates with prognosis, immune infiltration, and T cells exhaustion in lung adenocarcinoma |
| title_full | TOX correlates with prognosis, immune infiltration, and T cells exhaustion in lung adenocarcinoma |
| title_fullStr | TOX correlates with prognosis, immune infiltration, and T cells exhaustion in lung adenocarcinoma |
| title_full_unstemmed | TOX correlates with prognosis, immune infiltration, and T cells exhaustion in lung adenocarcinoma |
| title_short | TOX correlates with prognosis, immune infiltration, and T cells exhaustion in lung adenocarcinoma |
| title_sort | tox correlates with prognosis immune infiltration and t cells exhaustion in lung adenocarcinoma |
| topic | immune infiltration immunotherapy lung adenocarcinoma prognosis T cells exhaustion TOX |
| url | https://doi.org/10.1002/cam4.3324 |
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