Fibroblast growth factor receptor risk signature predicts patient prognosis and immunotherapy resistance in colorectal cancer
BackgroundFibroblast Growth Factor Receptor (FGFR) signaling is linked with tumor progression and tumor immunoevasion, yet the potential effect of FGFR signature on the prognosis of patient with colorectal cancer (CRC) and response to immune therapy remains elusive.MethodsThe fibroblast growth facto...
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Frontiers Media S.A.
2024-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1493673/full |
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| author | Xiaofang Li Zhiling Pan Zhiling Pan Tiankuo Luan Qian Xiao Liuying Li Qianxue Wu Guoqing Yao Xiang Zhang Daqiang Song |
| author_facet | Xiaofang Li Zhiling Pan Zhiling Pan Tiankuo Luan Qian Xiao Liuying Li Qianxue Wu Guoqing Yao Xiang Zhang Daqiang Song |
| author_sort | Xiaofang Li |
| collection | DOAJ |
| description | BackgroundFibroblast Growth Factor Receptor (FGFR) signaling is linked with tumor progression and tumor immunoevasion, yet the potential effect of FGFR signature on the prognosis of patient with colorectal cancer (CRC) and response to immune therapy remains elusive.MethodsThe fibroblast growth factor receptor risk signature (FRS) was identified through single-cell RNA sequencing, bulk RNA sequencing, and machine learning techniques. Signaling enrichment analyses were conducted using Gene Set Enrichment Analysis (GSEA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Drugs targeting the FRS were predicted using the Cancer Therapeutics Response Portal (CTRP) and PRISM databases. The analysis of T cell function and the tumor microenvironment (TME) was performed using flow cytometry.ResultsIn this study, we characterized the FRS in cancer patients with CRC. By integrating advanced techniques, we identified the FRS and revealed the intricate molecular landscape and diversity of the FRS within the TME. Notably, the FRS effectively predicted unfavorable prognosis and resistance to immunotherapy in CRC patients. Furthermore, PHA-793887, identified as a potential FRS inhibitor by the CTRP and PRISM databases, significantly restructured the immunosuppressive TME and enhanced the antitumor immune response, resulting in a reduced tumor burden in the MC38 murine tumor model.ConclusionTogether, these data support FRS positively correlates with poor prognosis and therapy resistance. The PHA-793887 could be a potential FRS inhibitor to improving the effectiveness of CRC management via bolstering antitumor immunity. |
| format | Article |
| id | doaj-art-ae3c46e9ef744f14a82ea19320463d1d |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-ae3c46e9ef744f14a82ea19320463d1d2025-08-20T02:07:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-11-011510.3389/fimmu.2024.14936731493673Fibroblast growth factor receptor risk signature predicts patient prognosis and immunotherapy resistance in colorectal cancerXiaofang Li0Zhiling Pan1Zhiling Pan2Tiankuo Luan3Qian Xiao4Liuying Li5Qianxue Wu6Guoqing Yao7Xiang Zhang8Daqiang Song9Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Operating Room, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, ChinaBaise Key Laboratory of Molecular Pathology in Tumors, Baise, ChinaChongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Vascular Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaBackgroundFibroblast Growth Factor Receptor (FGFR) signaling is linked with tumor progression and tumor immunoevasion, yet the potential effect of FGFR signature on the prognosis of patient with colorectal cancer (CRC) and response to immune therapy remains elusive.MethodsThe fibroblast growth factor receptor risk signature (FRS) was identified through single-cell RNA sequencing, bulk RNA sequencing, and machine learning techniques. Signaling enrichment analyses were conducted using Gene Set Enrichment Analysis (GSEA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Drugs targeting the FRS were predicted using the Cancer Therapeutics Response Portal (CTRP) and PRISM databases. The analysis of T cell function and the tumor microenvironment (TME) was performed using flow cytometry.ResultsIn this study, we characterized the FRS in cancer patients with CRC. By integrating advanced techniques, we identified the FRS and revealed the intricate molecular landscape and diversity of the FRS within the TME. Notably, the FRS effectively predicted unfavorable prognosis and resistance to immunotherapy in CRC patients. Furthermore, PHA-793887, identified as a potential FRS inhibitor by the CTRP and PRISM databases, significantly restructured the immunosuppressive TME and enhanced the antitumor immune response, resulting in a reduced tumor burden in the MC38 murine tumor model.ConclusionTogether, these data support FRS positively correlates with poor prognosis and therapy resistance. The PHA-793887 could be a potential FRS inhibitor to improving the effectiveness of CRC management via bolstering antitumor immunity.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1493673/fullfibroblasttumor immunityprognosistherapy resistancecolorectal cancer |
| spellingShingle | Xiaofang Li Zhiling Pan Zhiling Pan Tiankuo Luan Qian Xiao Liuying Li Qianxue Wu Guoqing Yao Xiang Zhang Daqiang Song Fibroblast growth factor receptor risk signature predicts patient prognosis and immunotherapy resistance in colorectal cancer Frontiers in Immunology fibroblast tumor immunity prognosis therapy resistance colorectal cancer |
| title | Fibroblast growth factor receptor risk signature predicts patient prognosis and immunotherapy resistance in colorectal cancer |
| title_full | Fibroblast growth factor receptor risk signature predicts patient prognosis and immunotherapy resistance in colorectal cancer |
| title_fullStr | Fibroblast growth factor receptor risk signature predicts patient prognosis and immunotherapy resistance in colorectal cancer |
| title_full_unstemmed | Fibroblast growth factor receptor risk signature predicts patient prognosis and immunotherapy resistance in colorectal cancer |
| title_short | Fibroblast growth factor receptor risk signature predicts patient prognosis and immunotherapy resistance in colorectal cancer |
| title_sort | fibroblast growth factor receptor risk signature predicts patient prognosis and immunotherapy resistance in colorectal cancer |
| topic | fibroblast tumor immunity prognosis therapy resistance colorectal cancer |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1493673/full |
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