Frontiers in Immunology (Apr 2024)
A three-gene expression score for predicting clinical benefit to anti-PD-1 blockade in advanced renal cell carcinoma
- 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
Affiliations
- Yoel Z. Betancor
- Translational 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, Spain
- Yoel Z. Betancor
- Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela (USC), Santiago de Compostela, Spain
- Miriam Ferreiro-Pantín
- Translational 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, Spain
- Urbano Anido-Herranz
- Translational 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, Spain
- Urbano Anido-Herranz
- Department of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela (USC), Santiago de Compostela, Spain
- Mar Fuentes-Losada
- Translational 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, Spain
- Mar Fuentes-Losada
- Department of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela (USC), Santiago de Compostela, Spain
- Luis León-Mateos
- Translational 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, Spain
- Luis León-Mateos
- Department of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela (USC), Santiago de Compostela, Spain
- Luis León-Mateos
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
- Silvia Margarita García-Acuña
- Department of Pathology, University Clinical Hospital of Santiago de Compostela, University of Santiago de Compostela (USC), Santiago de Compostela, Spain
- Vanessa Vaamonde-Rodríguez
- Department of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela (USC), Santiago de Compostela, Spain
- Beatriz García-Pinel
- Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela (USC), Santiago de Compostela, Spain
- Beatriz García-Pinel
- Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
- Víctor Cebey-López
- Translational 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, Spain
- Víctor Cebey-López
- Department of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela (USC), Santiago de Compostela, Spain
- Rosa Villaverde-Viaño
- Department of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela (USC), Santiago de Compostela, Spain
- Helena Lombardía-Rodríguez
- Translational 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, Spain
- Martin Kotrulev
- Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela (USC), Santiago de Compostela, Spain
- Martin Kotrulev
- Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
- Natalia Fernández-Díaz
- Translational 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, Spain
- Natalia Fernández-Díaz
- Department of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela (USC), Santiago de Compostela, Spain
- Iria Gomez-Tourino
- Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela (USC), Santiago de Compostela, Spain
- Iria Gomez-Tourino
- Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
- Carlos Fernández-Baltar
- Department of Urology, Complexo Hospitalario Universitario de Pontevedra, Pontevedra, Spain
- Jorge García-González
- Translational 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, Spain
- Jorge García-González
- Department of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela (USC), Santiago de Compostela, Spain
- Jorge García-González
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
- Jose M. C. Tubio
- Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela (USC), Santiago de Compostela, Spain
- Rafael López-López
- Translational 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, Spain
- Rafael López-López
- Department of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela (USC), Santiago de Compostela, Spain
- Rafael López-López
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
- Juan Ruiz-Bañobre
- Translational 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, Spain
- Juan Ruiz-Bañobre
- Department of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS), University of Santiago de Compostela (USC), Santiago de Compostela, Spain
- Juan Ruiz-Bañobre
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
- DOI
- https://doi.org/10.3389/fimmu.2024.1374728
- Journal volume & issue
-
Vol. 15
Abstract
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.
Keywords
