Association of lnc‐IL17RA‐11 with increased radiation sensitivity and improved prognosis of HPV‐positive HNSCC

Abstract

Human papillomavirus (HPV) associated head and neck squamous cell carcinoma (HNSCC) has a far better prognosis than HPV negative HNSCC. Recent studies suggest that long noncoding RNA (lncRNA) moieties may play a role in HPV associated differential HNSCC prognoses. In this study, we examined differential expression of lncRNAs in HPV+ vs HPV− HNSCC using The Cancer Genome Atlas database. LncRNAs were categorized based on expression level and survival analysis. A group of eight lncRNAs was identified in which altered expression was associated with both HPV infection and better prognosis. Subsequently, genes coexpressed with these lncRNAs in HNSCC cells were sorted into corresponding co‐expression modules. The lnc‐IL17RA‐11 coexpression module exhibited the greatest correlation with HPV infection and radiotherapy efficacy. We identified the lnc‐IL17RA‐11 transcription factor ER‐alpha as the most likely HPV infection associated factor promoting increased lnc‐IL17RA‐11 levels. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed enrichment among lnc‐IL17RA‐11 co‐expressed genes for functions related to DNA replication and cell proliferation. These observations are consistent with a model in which HPV infection upregulates transcription factor ER‐alpha, which increases levels of lnc‐IL17RA‐11 and coexpressed genes that promote HNSCC cell sensitivity to radiotherapy, thereby improving disease prognosis.

Characteristics of B lymphocyte infiltration in HPV+ head and neck squamous cell carcinoma

“…RNA‐seq and array data were analyzed using the R packages DESeq2 and limma respectively. Gene expression landscape associated with key mRNAs and co‐expressed genes was identified using weighted gene co‐expression network analysis (WGCNA) 19 . Function annotations were performed using DAVID (Version 6.8) (https://david.ncifcrf.gov) and KEGG (Kyoto Encyclopedia of Genes and Genomes) databases.…”

PRINS lncRNA Is a New Biomarker Candidate for HPV Infection and Prognosis of Head and Neck Squamous Cell Carcinomas

“…However, there is still a lack of comprehensive knowledge of how HPV infection regulates lncRNA expression or the general effect of these phenomena in tumor progression. A few lncRNAs that are closely related to HPV infection and the oncogenesis of HNSCC have been described and could have potential as biomarkers [ 22 , 23 , 24 , 25 , 26 ].…”

Cellular heterogeneity landscape in laryngeal squamous cell carcinoma

“…The differentially expressed genes of each cell cluster were identified by Wilcoxon rank‐sum test and were sorted by log‐fold change (Table S4). Identification of coexpression marker genes in each cell cluster was performed by WGCNA 21 (weighted gene coexpression network analysis) as described previously 22 . Putative cell‐cell interactions among normal, immune and tumor cells were mapped using a list of 708 unique ligands and 691 unique receptors forming a combined 2557 potential interaction pairs 23 .…”

“…performed by WGCNA 21 (weighted gene coexpression network analysis) as described previously. 22 Putative cell-cell interactions among normal, immune and tumor cells were mapped using a list of 708 unique ligands and 691 unique receptors forming a combined 2557 potential interaction pairs. 23 Putative cell-cycle phase analysis was performed by scran R. 24 2.6 | IHC staining IHC was conducted as described previously.…”