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pmid:36147910

Mesenchymal gene expression subtyping analysis for early-stage human papillomavirus-negative head and neck squamous cell carcinoma reveals prognostic and predictive applications.

Gregory M Mayhew · Joshua M Uronis · David Neil Hayes · Jose P Zevallos

Frontiers in oncology · 2022 doi:10.3389/fonc.2022.954037

Paper

complete

Experiment

complete

Data

partial

Analysis

complete

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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title
Mesenchymal gene expression subtyping analysis for early-stage human papillomavirus-negative head and neck squamous cell carcinoma reveals prognostic and predictive applications.
doi
10.3389/fonc.2022.954037
pmid
36147910
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[0]
Gregory M Mayhew
[1]
Joshua M Uronis
[2]
David Neil Hayes
[3]
Jose P Zevallos
journal
Frontiers in oncology
year
2022
abstract
Patients with oral cavity squamous cell carcinoma (OCSCC) are predominantly human papillomavirus (HPV)(-), and treatment typically involves surgical resection ± neck dissection, followed by radiation ± chemotherapy. We previously described four mRNA expression patterns (classical, atypical, basal, and mesenchymal), each with unique genomic features and prognosis. Here, we examine the clinical utility of gene expression subtyping in head and neck squamous cell carcinoma (HNSCC) and introduce potentially predictive applications in HPV(-) OCSCC. A retrospective genomic database analysis was performed including 562 HNSCC patients from MD Anderson (MDA-GSE41116) and The Cancer Genome Atlas (TCGA). Samples were assigned molecular subtypes (classical, atypical, basal, and mesenchymal) using an 88-gene classifier. HPV status was determined by gene expression. The clinical endpoint was overall survival censured at 36 months. The Kaplan-Meier plots and log-rank tests were used to investigate associations between clinical variables and survival. Of the 418 TCGA training patients who met analysis criteria, nearly 20% presented as stage I/II. Among node(-) OCSCC patients, the mesenchymal subtype is associated with worse survival (hazard ratio (HR) = 2.4, p = 0.021), offering a potentially actionable biomarker in otherwise early-stage, low-risk disease. This was confirmed in the MDA validation cohort. Node(-) non-mesenchymal OCSCC patients had far better survival compared to node(-) mesenchymal, and all node(+) patients had similarly poor survival. These findings suggest that the mesenchymal subtype is associated with poor survival in surgically resected, early-stage, node(-) OCSCC otherwise expected to have favorable outcomes. These findings highlight the potential value of gene expression subtyping as a pathology adjunct for prognostication and treatment decision-making in OCSCC patients.
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The Kaplan–Meier plots and the log-rank test were used to assess univariate associations between survival and study parameters. Cox models were used to check associations with adjustment for potential confounders.
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The Kaplan–Meier plots and the log-rank test were used to assess univariate associations between survival and study parameters. Cox models were used to check associations with adjustment for potential confounders.
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The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.
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Among node(−) OCSCC patients, the mesenchymal subtype is associated with worse survival (hazard ratio (HR) = 2.4, p = 0.021), offering a potentially actionable biomarker in otherwise early-stage, low-risk disease.
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Among node(−) OCSCC patients, the mesenchymal subtype is associated with worse survival (hazard ratio (HR) = 2.4, p = 0.021), offering a potentially actionable biomarker in otherwise early-stage, low-risk disease.
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sections[0] "Abstract" paragraph 1
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Among node(−) OCSCC patients, the mesenchymal subtype is associated with worse survival (hazard ratio (HR) = 2.4, p = 0.021), offering a potentially actionable biomarker in otherwise early-stage, low-risk disease.
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Among node(−) OCSCC patients, the mesenchymal subtype is associated with worse survival (hazard ratio (HR) = 2.4, p = 0.021), offering a potentially actionable biomarker in otherwise early-stage, low-risk disease.
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Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers (mRNA)
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