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).
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.
Results: LC had a higher mutational burden than OC and OPC (p <10). 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.
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.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105260 | DOI Listing |
J Transl Med
January 2025
Emergency Department, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, China.
Background: Acute respiratory distress syndrome (ARDS) is a life-threatening and heterogeneous disorder leading to lung injury. To date, effective therapies for ARDS remain limited. Sepsis is a frequent inducer of ARDS.
View Article and Find Full Text PDFGut Microbes
December 2025
Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA.
Here, we report that small extracellular vesicles (sEVs) in milk mediate the communication between bacteria and animal kingdoms, increase the divergence of bacteria in the intestine, and alter metabolite production by bacteria. We show that bovine milk sEVs select approximately 55,000 genomic variants in 19 species of bacteria from the murine cecum . The genomic variants are transcribed into mRNA.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Department of Human Nutrition, Ohio State University, Columbus, OH, 43210; Department of Molecular Genetics, Ohio State University, Columbus, OH, 43210; Center for RNA Biology, Ohio State University, Columbus, OH, 43210.
Zinc is an essential micronutrient that serves as a cofactor in a wide variety of enzymes, including Cu-Zn Superoxide Dismutase 1 (Sod1). We have discovered in Schizosaccharomyces pombe that Sod1 mRNA and protein levels are regulated in response to cellular zinc availability. We demonstrate that lower levels of Sod1 mRNA and protein accumulate under low zinc conditions, and that this regulation does not require the sod1 promoter or known factors that regulate transcription of sod1 in response to zinc and other environmental stresses.
View Article and Find Full Text PDFGene
January 2025
Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Object: N6-methyladenosine (mA), is well known as the most abundant epigenetic modification in messenger RNA, but its influence on laryngeal squamous cell carcinoma (LSCC) remains largely unexplored and poorly understood. This study was designed to explore the effects of mA on WISP1-mediated epithelial-mesenchymal transition (EMT) and tumorigenesis in LSCC.
Methods: mA methylated and expression levels of WISP1 in LSCC tumor tissues and cells were measured by MeRIP-qPCR, qRT-PCR, and western blotting.
Noncoding RNA Res
April 2025
Department of Anatomy, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Cardiovascular diseases (CVDs) are the primary cause of death globally. The evolution of nearly all types of CVDs is characterized by a common theme: the emergence of cardiac fibrosis. The precise mechanisms that trigger cardiac fibrosis are still not completely understood.
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