Molecular correlates for HPV-negative head and neck cancer engraftment prognosticate patient outcomes

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 () and Thomas Kislinger ()
Additional contact information
Matthew Waas: University Health Network
Christina Karamboulas: University Health Network
Benson Z. Wu: University Health Network
Shahbaz Khan: University Health Network
Stephanie Poon: University Health Network
Jalna Meens: University Health Network
Meinusha Govindarajan: University Health Network
Amanda Khoo: University Health Network
Salvador Mejia-Guerrero: University Health Network
Annie Ha: University Health Network
Lydia Y. Liu: University Health Network
Kevin C. J. Nixon: University Health Network
Joseph Walton: University Health Network
Scott V. Bratman: University of Toronto
Shao Hui Huang: University of Toronto
David Goldstein: and University of Toronto
Federico Gaiti: University Health Network
Laurie Ailles: University Health Network
Thomas Kislinger: University Health Network

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-55203-z

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