A three-gene expression score for predicting clinical benefit to anti-PD-1 blockade in advanced renal cell carcinoma
In the advanced renal cell carcinoma (RCC) scenario, there are no consistent biomarkers to predict the clinical benefit patients derived from immune checkpoint blockade (ICB). Taking this into consideration, herein, we conducted a retrospective study in order to develop and validate a gene expressio...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1374728/full |
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| author | Yoel Z. Betancor Yoel Z. Betancor Miriam Ferreiro-Pantín Urbano Anido-Herranz Urbano Anido-Herranz Mar Fuentes-Losada Mar Fuentes-Losada Luis León-Mateos Luis León-Mateos Luis León-Mateos Silvia Margarita García-Acuña Vanessa Vaamonde-Rodríguez Beatriz García-Pinel Beatriz García-Pinel Víctor Cebey-López Víctor Cebey-López Rosa Villaverde-Viaño Helena Lombardía-Rodríguez Martin Kotrulev Martin Kotrulev Natalia Fernández-Díaz Natalia Fernández-Díaz Iria Gomez-Tourino Iria Gomez-Tourino Carlos Fernández-Baltar Jorge García-González Jorge García-González Jorge García-González Jose M. C. Tubio Rafael López-López Rafael López-López Rafael López-López Juan Ruiz-Bañobre Juan Ruiz-Bañobre Juan Ruiz-Bañobre |
| author_facet | Yoel Z. Betancor Yoel Z. Betancor Miriam Ferreiro-Pantín Urbano Anido-Herranz Urbano Anido-Herranz Mar Fuentes-Losada Mar Fuentes-Losada Luis León-Mateos Luis León-Mateos Luis León-Mateos Silvia Margarita García-Acuña Vanessa Vaamonde-Rodríguez Beatriz García-Pinel Beatriz García-Pinel Víctor Cebey-López Víctor Cebey-López Rosa Villaverde-Viaño Helena Lombardía-Rodríguez Martin Kotrulev Martin Kotrulev Natalia Fernández-Díaz Natalia Fernández-Díaz Iria Gomez-Tourino Iria Gomez-Tourino Carlos Fernández-Baltar Jorge García-González Jorge García-González Jorge García-González Jose M. C. Tubio Rafael López-López Rafael López-López Rafael López-López Juan Ruiz-Bañobre Juan Ruiz-Bañobre Juan Ruiz-Bañobre |
| author_sort | Yoel Z. Betancor |
| collection | DOAJ |
| description | In the advanced renal cell carcinoma (RCC) scenario, there are no consistent biomarkers to predict the clinical benefit patients derived from immune checkpoint blockade (ICB). Taking this into consideration, herein, we conducted a retrospective study in order to develop and validate a gene expression score for predicting clinical benefit to the anti-PD-1 antibody nivolumab in the context of patients diagnosed with advanced clear cell RCC enrolled in the CheckMate-009, CheckMate-010, and CheckMate-025 clinical trials. First, a three-gene expression score (3GES) with prognostic value for overall survival integrating HMGA1, NUP62, and ARHGAP42 transcripts was developed in a cohort of patients treated with nivolumab. Its prognostic value was then validated in the TCGA-KIRC cohort. Second, the predictive value for nivolumab was confirmed in a set of patients from the CheckMate-025 phase 3 clinical trial. Lastly, we explored the correlation of our 3GES with different clinical, molecular, and immune tumor characteristics. If the results of this study are definitively validated in other retrospective and large-scale, prospective studies, the 3GES will represent a valuable tool for guiding the design of ICB-based clinical trials in the aRCC scenario in the near future. |
| first_indexed | 2024-04-24T11:36:05Z |
| format | Article |
| id | doaj.art-3df50f215da44f60a777ca651a4ba236 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-24T11:36:05Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3df50f215da44f60a777ca651a4ba2362024-04-10T05:20:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-04-011510.3389/fimmu.2024.13747281374728A three-gene expression score for predicting clinical benefit to anti-PD-1 blockade in advanced renal cell carcinomaYoel Z. Betancor0Yoel Z. Betancor1Miriam Ferreiro-Pantín2Urbano Anido-Herranz3Urbano Anido-Herranz4Mar Fuentes-Losada5Mar Fuentes-Losada6Luis León-Mateos7Luis León-Mateos8Luis León-Mateos9Silvia Margarita García-Acuña10Vanessa Vaamonde-Rodríguez11Beatriz García-Pinel12Beatriz García-Pinel13Víctor Cebey-López14Víctor Cebey-López15Rosa Villaverde-Viaño16Helena Lombardía-Rodríguez17Martin Kotrulev18Martin Kotrulev19Natalia Fernández-Díaz20Natalia Fernández-Díaz21Iria Gomez-Tourino22Iria Gomez-Tourino23Carlos Fernández-Baltar24Jorge García-González25Jorge García-González26Jorge García-González27Jose M. C. Tubio28Rafael López-López29Rafael López-López30Rafael López-López31Juan Ruiz-Bañobre32Juan Ruiz-Bañobre33Juan Ruiz-Bañobre34Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago de Compostela, University of Santiago de Compostela (USC), Santiago de Compostela, SpainCentre for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela (USC), Santiago de Compostela, SpainTranslational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago de Compostela, University of Santiago de Compostela (USC), Santiago de Compostela, SpainTranslational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago de Compostela, University of Santiago de Compostela (USC), Santiago de Compostela, SpainDepartment of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela (USC), Santiago de Compostela, SpainTranslational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago de Compostela, University of Santiago de Compostela (USC), Santiago de Compostela, SpainDepartment of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela (USC), Santiago de Compostela, SpainTranslational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago de Compostela, University of Santiago de Compostela (USC), Santiago de Compostela, SpainDepartment of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela (USC), Santiago de Compostela, SpainCentro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, SpainDepartment of Pathology, University Clinical Hospital of Santiago de Compostela, University of Santiago de Compostela (USC), Santiago de Compostela, SpainDepartment of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela (USC), Santiago de Compostela, SpainCentre for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela (USC), Santiago de Compostela, SpainHealth Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, SpainTranslational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago de Compostela, University of Santiago de Compostela (USC), Santiago de Compostela, SpainDepartment of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela (USC), Santiago de Compostela, SpainDepartment of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela (USC), Santiago de Compostela, SpainTranslational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago de Compostela, University of Santiago de Compostela (USC), Santiago de Compostela, SpainCentre for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela (USC), Santiago de Compostela, SpainHealth Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, SpainTranslational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago de Compostela, University of Santiago de Compostela (USC), Santiago de Compostela, SpainDepartment of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela (USC), Santiago de Compostela, SpainCentre for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela (USC), Santiago de Compostela, SpainHealth Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, SpainDepartment of Urology, Complexo Hospitalario Universitario de Pontevedra, Pontevedra, SpainTranslational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago de Compostela, University of Santiago de Compostela (USC), Santiago de Compostela, SpainDepartment of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela (USC), Santiago de Compostela, SpainCentro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, SpainCentre for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela (USC), Santiago de Compostela, SpainTranslational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago de Compostela, University of Santiago de Compostela (USC), Santiago de Compostela, SpainDepartment of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela (USC), Santiago de Compostela, SpainCentro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, SpainTranslational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago de Compostela, University of Santiago de Compostela (USC), Santiago de Compostela, SpainDepartment of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela (USC), Santiago de Compostela, SpainCentro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, SpainIn the advanced renal cell carcinoma (RCC) scenario, there are no consistent biomarkers to predict the clinical benefit patients derived from immune checkpoint blockade (ICB). Taking this into consideration, herein, we conducted a retrospective study in order to develop and validate a gene expression score for predicting clinical benefit to the anti-PD-1 antibody nivolumab in the context of patients diagnosed with advanced clear cell RCC enrolled in the CheckMate-009, CheckMate-010, and CheckMate-025 clinical trials. First, a three-gene expression score (3GES) with prognostic value for overall survival integrating HMGA1, NUP62, and ARHGAP42 transcripts was developed in a cohort of patients treated with nivolumab. Its prognostic value was then validated in the TCGA-KIRC cohort. Second, the predictive value for nivolumab was confirmed in a set of patients from the CheckMate-025 phase 3 clinical trial. Lastly, we explored the correlation of our 3GES with different clinical, molecular, and immune tumor characteristics. If the results of this study are definitively validated in other retrospective and large-scale, prospective studies, the 3GES will represent a valuable tool for guiding the design of ICB-based clinical trials in the aRCC scenario in the near future.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1374728/fullnivolumabbiomarkergene expressionimmunotherapykidney cancer |
| spellingShingle | Yoel Z. Betancor Yoel Z. Betancor Miriam Ferreiro-Pantín Urbano Anido-Herranz Urbano Anido-Herranz Mar Fuentes-Losada Mar Fuentes-Losada Luis León-Mateos Luis León-Mateos Luis León-Mateos Silvia Margarita García-Acuña Vanessa Vaamonde-Rodríguez Beatriz García-Pinel Beatriz García-Pinel Víctor Cebey-López Víctor Cebey-López Rosa Villaverde-Viaño Helena Lombardía-Rodríguez Martin Kotrulev Martin Kotrulev Natalia Fernández-Díaz Natalia Fernández-Díaz Iria Gomez-Tourino Iria Gomez-Tourino Carlos Fernández-Baltar Jorge García-González Jorge García-González Jorge García-González Jose M. C. Tubio Rafael López-López Rafael López-López Rafael López-López Juan Ruiz-Bañobre Juan Ruiz-Bañobre Juan Ruiz-Bañobre A three-gene expression score for predicting clinical benefit to anti-PD-1 blockade in advanced renal cell carcinoma Frontiers in Immunology nivolumab biomarker gene expression immunotherapy kidney cancer |
| title | A three-gene expression score for predicting clinical benefit to anti-PD-1 blockade in advanced renal cell carcinoma |
| title_full | A three-gene expression score for predicting clinical benefit to anti-PD-1 blockade in advanced renal cell carcinoma |
| title_fullStr | A three-gene expression score for predicting clinical benefit to anti-PD-1 blockade in advanced renal cell carcinoma |
| title_full_unstemmed | A three-gene expression score for predicting clinical benefit to anti-PD-1 blockade in advanced renal cell carcinoma |
| title_short | A three-gene expression score for predicting clinical benefit to anti-PD-1 blockade in advanced renal cell carcinoma |
| title_sort | three gene expression score for predicting clinical benefit to anti pd 1 blockade in advanced renal cell carcinoma |
| topic | nivolumab biomarker gene expression immunotherapy kidney cancer |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1374728/full |
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