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Claudin-1 in Head and Neck Squamous Cell Carcinoma

  • 0Head and Neck Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Oncology +

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September 4, 2024

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September 4, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

High Claudin-1 (CLDN1) expression in head and neck squamous cell carcinoma (HNSCC) indicates a poorer prognosis. Targeting CLDN1 may improve immunotherapy response in HNSCC patients.

Area Of Science

  • Oncology
  • Molecular Biology
  • Immunotherapy

Background

  • Limited response to immunotherapy in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).
  • Prognostic factors for HNSCC are scarce, with gene expression signatures showing promise but limited clinical use.
  • Claudin-1 (CLDN1) influences tumor microenvironment and immune infiltration, with high expression in HNSCC.

Purpose Of The Study

  • To investigate the prognostic significance of Claudin-1 (CLDN1) expression in head and neck squamous cell carcinoma (HNSCC).
  • To explore the relationship between CLDN1 expression and tumor characteristics, including transcriptomic clusters and HPV status.
  • To evaluate CLDN1 as a potential therapeutic target in HNSCC.

Main Methods

  • Analysis of a single-center cohort of 100 loco-regionally advanced HNSCC patients.
  • Gene expression (GE) analysis using Affymetrix ClariomD chips on primary tumor specimens.
  • Primary endpoint: overall survival (OS); secondary endpoint: disease-free survival (DFS).

Main Results

  • Higher CLDN1 expression was significantly associated with shorter overall survival (OS) (HR: 3, p = 0.0023) and disease-free survival (DFS) (HR: 2.14, p = 0.02).
  • CLDN1 expression varied by primary site, highest in hypopharynx cancers, and correlated with mesenchymal and hypoxic transcriptomic clusters.
  • No significant differences in CLDN1 expression were observed based on HPV status or clinical stage.

Conclusions

  • CLDN1 expression is heterogeneous in HNSCC and serves as a significant negative prognostic factor.
  • High CLDN1 is linked to HPV-like biology and hypoxic environments, while low CLDN1 is associated with immune-sensitive clusters.
  • Targeting CLDN1, potentially in combination with immunotherapy, could enhance treatment outcomes for HNSCC patients.

Keywords:

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