Molecular Correlates for HPV-negative Head and Neck Cancer Engraftment Prognosticate Patient Outcomes

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Dec 31

PMID 39738080

Authors

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

Affiliations

Soon will be listed here.

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.

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