Document Type

Article

Publication Date

6-18-2024

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This article, first published by Frontiers Media, is the author's final published version in Frontiers in Oncology, Volume 14, 2024, Article number 1412212.

The published version is available at https://doi.org/10.3389/fonc.2024.1412212.

Copyright © 2024 Estephan, Kumar, Stewart, Banoub, Linnenbach, Harshyne, Martinez-Outschoorn, Mahoney, Curry, Johnson, South and Luginbuhl

Abstract

INTRODUCTION: Oral cavity squamous cell carcinoma (OSCC) occurs most frequently in patients >60 years old with a history of tobacco and alcohol use. Epidemiological studies describe increased incidence of OSCC in younger adults (years). Despite its poor prognosis, knowledge of OSCC tumor microenvironment (TME) characteristics in younger adults is scarce and could help inform possible resistance to emerging treatment options.

METHODS: Patients with OSCC were evaluated using TCGA-HNSC (n=121) and a stage and subsite-matched institutional cohort (n=8) to identify differential gene expression focusing on the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT) processes in younger (≤45 years) vs. older adults (≥60 years). NanoString nCounter analysis was performed using isolated total RNA from formalin-fixed paraffin-embedded (FFPE) tumor samples. Stained tumor slides from young and old OSCC patients were evaluated for CD8+ T-cell counts using immunohistochemistry.

RESULTS: Younger OSCC patients demonstrated significantly increased expression of ECM remodeling and EMT process genes, as well as TME immunosuppression. Gene set enrichment analyses demonstrated increased ECM pathways and concurrent decreased immune pathways in young relative to old patients. Transcripts per million of genetic markers involved in ECM remodeling including LAMB3, VCAN, S100A9, COL5A1, and ITGB2 were significantly increased in tumors of younger vs. older patients (adjusted p-value < 0.10). Young patient TMEs demonstrated a 2.5-fold reduction in CD8+ T-cells as compared to older patients (p < 0.05).

CONCLUSION: Differential gene expression impacting ECM remodeling and TME immunosuppression may contribute to disease progression in younger adult OSCC and has implications on response to evolving treatment modalities, such as immune checkpoint inhibitor therapy.

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Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Additional Files
Supplementary File.docx (65 kB)

PubMed ID

38957320

Language

English

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