Transcriptome of Tumor-Infiltrating T Cells in Colorectal Cancer Patients Uncovered a Unique Gene Signature in CD4+ T Cells Associated with Poor Disease-Specific Survival
<p dir="ltr">Colorectal cancer (CRC) is influenced by infiltration of immune cell populations in the tumor microenvironment. While elevated levels of cytotoxic T cells are associated with improved prognosis, limited studies have reported associations between CD4<sup>+</sup&g...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , , , , , |
| منشور في: |
2021
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| _version_ | 1864513516718784512 |
|---|---|
| author | Salman M. Toor (8854751) |
| author2 | Varun Sasidharan Nair (5396393) Reem Saleh (3513056) Rowaida Z. Taha (8854754) Khaled Murshed (8309781) Mahmood Al-Dhaheri (9621035) Mahwish Khawar (9621038) Ayman A. Ahmed (18513762) Mohamed A. Kurer (18513765) Mohamed Abu Nada (8309784) Eyad Elkord (5396390) |
| author2_role | author author author author author author author author author author |
| author_facet | Salman M. Toor (8854751) Varun Sasidharan Nair (5396393) Reem Saleh (3513056) Rowaida Z. Taha (8854754) Khaled Murshed (8309781) Mahmood Al-Dhaheri (9621035) Mahwish Khawar (9621038) Ayman A. Ahmed (18513762) Mohamed A. Kurer (18513765) Mohamed Abu Nada (8309784) Eyad Elkord (5396390) |
| author_role | author |
| dc.creator.none.fl_str_mv | Salman M. Toor (8854751) Varun Sasidharan Nair (5396393) Reem Saleh (3513056) Rowaida Z. Taha (8854754) Khaled Murshed (8309781) Mahmood Al-Dhaheri (9621035) Mahwish Khawar (9621038) Ayman A. Ahmed (18513762) Mohamed A. Kurer (18513765) Mohamed Abu Nada (8309784) Eyad Elkord (5396390) |
| dc.date.none.fl_str_mv | 2021-04-01T00:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3390/vaccines9040334 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Transcriptome_of_Tumor-Infiltrating_T_Cells_in_Colorectal_Cancer_Patients_Uncovered_a_Unique_Gene_Signature_in_CD4_T_Cells_Associated_with_Poor_Disease-Specific_Survival/25764861 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Immunology Oncology and carcinogenesis colorectal cancer tumor microenvironment T cells transcriptomics |
| dc.title.none.fl_str_mv | Transcriptome of Tumor-Infiltrating T Cells in Colorectal Cancer Patients Uncovered a Unique Gene Signature in CD4+ T Cells Associated with Poor Disease-Specific Survival |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Colorectal cancer (CRC) is influenced by infiltration of immune cell populations in the tumor microenvironment. While elevated levels of cytotoxic T cells are associated with improved prognosis, limited studies have reported associations between CD4<sup>+</sup> T cells and disease outcomes. We recently performed transcriptomic profiling and comparative analyses of sorted CD4<sup>+</sup> and CD8<sup>+</sup> tumor-infiltrating lymphocytes (TILs) from bulk tumors of CRC patients with varying disease stages. In this study, we compared the transcriptomes of CD4<sup>+</sup> with CD8<sup>+</sup> TILs. Functional annotation pathway analyses revealed the downregulation of inflammatory response-related genes, while T cell activation and angiogenesis-related genes were upregulated in CD4<sup>+</sup> TILs. The top 200 deregulated genes in CD4<sup>+</sup> TILs were aligned with the cancer genome atlas (TCGA) CRC dataset to identify a unique gene signature associated with poor prognosis. Moreover, 69 upregulated and 20 downregulated genes showed similar trends of up/downregulation in the TCGA dataset and were used to calculate “poor prognosis score” (ppScore), which was significantly associated with disease-specific survival. High ppScore patients showed lower expression of Treg-, Th1-, and Th17-related genes, and higher expression of Th2-related genes. Our data highlight the significance of T cells within the TME and identify a unique candidate prognostic gene signature for CD4<sup>+</sup> TILs in CRC patients.</p><p><br></p><h2>Other Information</h2><p dir="ltr">Published in: Vaccines<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/vaccines9040334" target="_blank">https://dx.doi.org/10.3390/vaccines9040334</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_1bde28cbeb7d6bfdbf6bd5c6224ee742 |
| identifier_str_mv | 10.3390/vaccines9040334 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25764861 |
| publishDate | 2021 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Transcriptome of Tumor-Infiltrating T Cells in Colorectal Cancer Patients Uncovered a Unique Gene Signature in CD4+ T Cells Associated with Poor Disease-Specific SurvivalSalman M. Toor (8854751)Varun Sasidharan Nair (5396393)Reem Saleh (3513056)Rowaida Z. Taha (8854754)Khaled Murshed (8309781)Mahmood Al-Dhaheri (9621035)Mahwish Khawar (9621038)Ayman A. Ahmed (18513762)Mohamed A. Kurer (18513765)Mohamed Abu Nada (8309784)Eyad Elkord (5396390)Biomedical and clinical sciencesImmunologyOncology and carcinogenesiscolorectal cancertumor microenvironmentT cellstranscriptomics<p dir="ltr">Colorectal cancer (CRC) is influenced by infiltration of immune cell populations in the tumor microenvironment. While elevated levels of cytotoxic T cells are associated with improved prognosis, limited studies have reported associations between CD4<sup>+</sup> T cells and disease outcomes. We recently performed transcriptomic profiling and comparative analyses of sorted CD4<sup>+</sup> and CD8<sup>+</sup> tumor-infiltrating lymphocytes (TILs) from bulk tumors of CRC patients with varying disease stages. In this study, we compared the transcriptomes of CD4<sup>+</sup> with CD8<sup>+</sup> TILs. Functional annotation pathway analyses revealed the downregulation of inflammatory response-related genes, while T cell activation and angiogenesis-related genes were upregulated in CD4<sup>+</sup> TILs. The top 200 deregulated genes in CD4<sup>+</sup> TILs were aligned with the cancer genome atlas (TCGA) CRC dataset to identify a unique gene signature associated with poor prognosis. Moreover, 69 upregulated and 20 downregulated genes showed similar trends of up/downregulation in the TCGA dataset and were used to calculate “poor prognosis score” (ppScore), which was significantly associated with disease-specific survival. High ppScore patients showed lower expression of Treg-, Th1-, and Th17-related genes, and higher expression of Th2-related genes. Our data highlight the significance of T cells within the TME and identify a unique candidate prognostic gene signature for CD4<sup>+</sup> TILs in CRC patients.</p><p><br></p><h2>Other Information</h2><p dir="ltr">Published in: Vaccines<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/vaccines9040334" target="_blank">https://dx.doi.org/10.3390/vaccines9040334</a></p>2021-04-01T00:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/vaccines9040334https://figshare.com/articles/journal_contribution/Transcriptome_of_Tumor-Infiltrating_T_Cells_in_Colorectal_Cancer_Patients_Uncovered_a_Unique_Gene_Signature_in_CD4_T_Cells_Associated_with_Poor_Disease-Specific_Survival/25764861CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/257648612021-04-01T00:00:00Z |
| spellingShingle | Transcriptome of Tumor-Infiltrating T Cells in Colorectal Cancer Patients Uncovered a Unique Gene Signature in CD4+ T Cells Associated with Poor Disease-Specific Survival Salman M. Toor (8854751) Biomedical and clinical sciences Immunology Oncology and carcinogenesis colorectal cancer tumor microenvironment T cells transcriptomics |
| status_str | publishedVersion |
| title | Transcriptome of Tumor-Infiltrating T Cells in Colorectal Cancer Patients Uncovered a Unique Gene Signature in CD4+ T Cells Associated with Poor Disease-Specific Survival |
| title_full | Transcriptome of Tumor-Infiltrating T Cells in Colorectal Cancer Patients Uncovered a Unique Gene Signature in CD4+ T Cells Associated with Poor Disease-Specific Survival |
| title_fullStr | Transcriptome of Tumor-Infiltrating T Cells in Colorectal Cancer Patients Uncovered a Unique Gene Signature in CD4+ T Cells Associated with Poor Disease-Specific Survival |
| title_full_unstemmed | Transcriptome of Tumor-Infiltrating T Cells in Colorectal Cancer Patients Uncovered a Unique Gene Signature in CD4+ T Cells Associated with Poor Disease-Specific Survival |
| title_short | Transcriptome of Tumor-Infiltrating T Cells in Colorectal Cancer Patients Uncovered a Unique Gene Signature in CD4+ T Cells Associated with Poor Disease-Specific Survival |
| title_sort | Transcriptome of Tumor-Infiltrating T Cells in Colorectal Cancer Patients Uncovered a Unique Gene Signature in CD4+ T Cells Associated with Poor Disease-Specific Survival |
| topic | Biomedical and clinical sciences Immunology Oncology and carcinogenesis colorectal cancer tumor microenvironment T cells transcriptomics |