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All HPV-negative head and neck cancers are not the same: Analysis of the TCGA dataset reveals that anatomical sites have distinct mutation, transcriptome, hypoxia, and tumor microenvironment profiles.

Authors :
Kim HAJ
Zeng PYF
Shaikh MH
Mundi N
Ghasemi F
Di Gravio E
Khan H
MacNeil D
Khan MI
Patel K
Mendez A
Yoo J
Fung K
Lang P
Palma DA
Mymryk JS
Barrett JW
Boutros PC
Nichols AC
Source :
Oral oncology [Oral Oncol] 2021 May; Vol. 116, pp. 105260. Date of Electronic Publication: 2021 Mar 13.
Publication Year :
2021

Abstract

Purpose: Head and neck squamous cell carcinoma (HNSCC) affects various anatomical sites, which often dictates whether the cancer is managed with primary surgery or radiation. This study aimed to assess differences in single nucleotide variation (SNV), copy number, mRNA abundance, methylation, and tumor microenvironment (TME) between HPV-negative oral cavity (OC), oropharyngeal (OPC), hypopharyngeal (HPC), and laryngeal (LC) cancers within The Cancer Genome Atlas (TCGA).<br />Methods: We downloaded the clinical information and molecular data for the TCGA HNSCC cohort from the data portal and published literature. The TME was estimated using mRNA abundance data. We conducted our analyses within the Bioconductor statistical framework in the R environment. CNA and mRNA abundance results were correlated and grouped with SNV results for downstream pathway analysis.<br />Results: LC had a higher mutational burden than OC and OPC (p <10 <superscript>-4</superscript> ). LC tumors were enriched in CSMD3, NSD1, DCHS2 and ANK2 SNVs, while OC tumors were enriched in CASP8 SNVs (FDR < 0.1). LCs were enriched for neuronal and glycosylation pathways, while OCs were enriched for extracellular matrix pathways. B cells and endothelial cells were more abundant in LC while monocytes were more abundant in OC (FDR < 0.1). OPC was the most hypoxic, followed by OC then LC (FDR < 0.05). OC had greater methylation of Hox genes than LC. Subsite analysis revealed that oral tongue cancers had fewer CASP8 and FBN2 mutations and higher dendritic cell abundance than other oral cavity cancers.<br />Conclusions: We identified significant genomic, transcriptional, and microenvironmental differences between HPV-negative HNSCC. Further study is warranted to determine if these findings portend differential response to specific treatment modalities.<br /> (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1879-0593
Volume :
116
Database :
MEDLINE
Journal :
Oral oncology
Publication Type :
Academic Journal
Accession number :
33725617
Full Text :
https://doi.org/10.1016/j.oraloncology.2021.105260