头颈部鳞状细胞癌
生物
生物导体
肿瘤微环境
癌症研究
转录组
癌症
DNA甲基化
头颈部癌
肿瘤科
基因
遗传学
医学
基因表达
作者
Hugh Andrew Jinwook Kim,Peter YF. Zeng,Mushfiq Hassan Shaikh,Neil Mundi,Farhad Ghasemi,Eric Di Gravio,Halema Khan,S. Danielle MacNeil,Mohammed I. Khan,Krupal B. Patel,Adrian Mendez,John Yoo,Kevin Fung,Pencilla Lang,David A. Palma,Joe S. Mymryk,John W. Barrett,Paul C. Boutros,Anthony C. Nichols
出处
期刊:Oral Oncology
[Elsevier]
日期:2021-05-01
卷期号:116: 105260-105260
被引量:17
标识
DOI:10.1016/j.oraloncology.2021.105260
摘要
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).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.LC had a higher mutational burden than OC and OPC (p <10-4). 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.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.
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