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

• Published in: Nature communications 2024-12, Vol.15 (1), p.10869-14, Article 10869
• Main Authors: Waas, Matthew, Karamboulas, Christina, Wu, Benson Z., Khan, Shahbaz, Poon, Stephanie, Meens, Jalna, Govindarajan, Meinusha, Khoo, Amanda, Mejia-Guerrero, Salvador, Ha, Annie, Liu, Lydia Y., Nixon, Kevin C. J., Walton, Joseph, Bratman, Scott V., Huang, Shao Hui, Goldstein, David, Gaiti, Federico, Ailles, Laurie, Kislinger, Thomas
• Format: Article
• Language: English
• Subjects: 45/91; 631/553; 692/4028/67/1536/1665/3016; 692/53/2422; 82/1; 82/58; Aged; Animals; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer; Clinical outcomes; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Head & neck cancer; Head and neck carcinoma; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - virology; Human papillomavirus; Humanities and Social Sciences; Humans; Lymph nodes; Male; Mice; Middle Aged; multidisciplinary; Papillomaviridae; Papillomavirus Infections - virology; Patients; Phenotypes; Prognosis; Proteomics; Proteomics - methods; Science; Science (multidisciplinary); Side effects; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - genetics; Squamous Cell Carcinoma of Head and Neck - metabolism; Squamous Cell Carcinoma of Head and Neck - pathology; Squamous Cell Carcinoma of Head and Neck - virology; Transcriptome; Transcriptomics; Xenografts; Xenotransplantation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-55203-z

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. ‘Engraftment of patient-derived xenografts in samples from head and neck squamous cell carcinoma is variable. Here, the authors use transcriptomic and proteomic profiling to correlate engraftment of PDX with molecular phenotype, and validate LAMC2 and TGM3 as potential biomarkers of stratification.