Molecular correlates for HPV-negative head and neck cancer engraftment prognosticate patient outcomes
Abstract There is a pressing need to improve risk stratification and treatment selection for HPV-negative head and neck squamous cell carcinoma (HNSCC) due to the adverse side effects of treatment. One of the most important prognostic features is lymph nodes involvement. Previously, we demonstrated...
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55203-z |
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| author | Matthew Waas Christina Karamboulas Benson Z. Wu Shahbaz Khan Stephanie Poon Jalna Meens Meinusha Govindarajan Amanda Khoo Salvador Mejia-Guerrero Annie Ha Lydia Y. Liu Kevin C. J. Nixon Joseph Walton Scott V. Bratman Shao Hui Huang David Goldstein Federico Gaiti Laurie Ailles Thomas Kislinger |
| author_facet | Matthew Waas Christina Karamboulas Benson Z. Wu Shahbaz Khan Stephanie Poon Jalna Meens Meinusha Govindarajan Amanda Khoo Salvador Mejia-Guerrero Annie Ha Lydia Y. Liu Kevin C. J. Nixon Joseph Walton Scott V. Bratman Shao Hui Huang David Goldstein Federico Gaiti Laurie Ailles Thomas Kislinger |
| author_sort | Matthew Waas |
| collection | DOAJ |
| description | Abstract There is a pressing need to improve risk stratification and treatment selection for HPV-negative head and neck squamous cell carcinoma (HNSCC) due to the adverse side effects of treatment. One of the most important prognostic features is lymph nodes involvement. Previously, we demonstrated that tumor formation in patient-derived xenografts (i.e. engraftment) was associated with poor clinical outcomes in patients with HPV-negative HNSCC. However, assessing engraftment is challenging in clinical settings. Here, we perform transcriptomic and proteomic profiling of 88 HNSCC patients and find the relationship between engraftment and clinical outcomes is recapitulated by molecular phenotype. We identify LAMC2 and TGM3 as candidate prognostic biomarkers and validated their utility in an independent cohort containing 404 HPV-negative HNSCC patients. Strikingly, these markers significantly improve prediction of outcomes beyond nodal status alone and can significantly stratify patients without any nodal involvement. Overall, our study demonstrates how the molecular characteristics of engraftment can inform patient prognostication. |
| format | Article |
| id | doaj-art-da6c1e7041594a23b8083c9d31b9fbb3 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-da6c1e7041594a23b8083c9d31b9fbb32025-01-05T12:36:03ZengNature PortfolioNature Communications2041-17232024-12-0115111410.1038/s41467-024-55203-zMolecular correlates for HPV-negative head and neck cancer engraftment prognosticate patient outcomesMatthew Waas0Christina Karamboulas1Benson Z. Wu2Shahbaz Khan3Stephanie Poon4Jalna Meens5Meinusha Govindarajan6Amanda Khoo7Salvador Mejia-Guerrero8Annie Ha9Lydia Y. Liu10Kevin C. J. Nixon11Joseph Walton12Scott V. Bratman13Shao Hui Huang14David Goldstein15Federico Gaiti16Laurie Ailles17Thomas Kislinger18Princess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkDepartment of Medical Biophysics, University of TorontoRadiation Medicine Program, Princess Margaret Cancer Centre, and Department of Radiation Oncology, University of TorontoDepartment of Otolaryngology-Head and Neck Surgery, Princess Margaret Cancer Centre, and University of TorontoPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkPrincess Margaret Cancer Centre, University Health NetworkAbstract There is a pressing need to improve risk stratification and treatment selection for HPV-negative head and neck squamous cell carcinoma (HNSCC) due to the adverse side effects of treatment. One of the most important prognostic features is lymph nodes involvement. Previously, we demonstrated that tumor formation in patient-derived xenografts (i.e. engraftment) was associated with poor clinical outcomes in patients with HPV-negative HNSCC. However, assessing engraftment is challenging in clinical settings. Here, we perform transcriptomic and proteomic profiling of 88 HNSCC patients and find the relationship between engraftment and clinical outcomes is recapitulated by molecular phenotype. We identify LAMC2 and TGM3 as candidate prognostic biomarkers and validated their utility in an independent cohort containing 404 HPV-negative HNSCC patients. Strikingly, these markers significantly improve prediction of outcomes beyond nodal status alone and can significantly stratify patients without any nodal involvement. Overall, our study demonstrates how the molecular characteristics of engraftment can inform patient prognostication.https://doi.org/10.1038/s41467-024-55203-z |
| spellingShingle | Matthew Waas Christina Karamboulas Benson Z. Wu Shahbaz Khan Stephanie Poon Jalna Meens Meinusha Govindarajan Amanda Khoo Salvador Mejia-Guerrero Annie Ha Lydia Y. Liu Kevin C. J. Nixon Joseph Walton Scott V. Bratman Shao Hui Huang David Goldstein Federico Gaiti Laurie Ailles Thomas Kislinger Molecular correlates for HPV-negative head and neck cancer engraftment prognosticate patient outcomes Nature Communications |
| title | Molecular correlates for HPV-negative head and neck cancer engraftment prognosticate patient outcomes |
| title_full | Molecular correlates for HPV-negative head and neck cancer engraftment prognosticate patient outcomes |
| title_fullStr | Molecular correlates for HPV-negative head and neck cancer engraftment prognosticate patient outcomes |
| title_full_unstemmed | Molecular correlates for HPV-negative head and neck cancer engraftment prognosticate patient outcomes |
| title_short | Molecular correlates for HPV-negative head and neck cancer engraftment prognosticate patient outcomes |
| title_sort | molecular correlates for hpv negative head and neck cancer engraftment prognosticate patient outcomes |
| url | https://doi.org/10.1038/s41467-024-55203-z |
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