Abstract
Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease marked by frequent recurrence and metastasis and stagnant survival rates. To enhance molecular knowledge of HNSCC and define a non-coding RNA (ncRNA) landscape of the disease, we profiled the transcriptome-wide dysregulation of long non-coding RNA (lncRNA), microRNA (miRNA), and PIWI-interacting RNA (piRNA) using RNA-sequencing data from 422 HNSCC patients in The Cancer Genome Atlas (TCGA). 307 non-coding transcripts differentially expressed in HNSCC were significantly correlated with patient survival, and associated with mutations in TP53, CDKN2A, CASP8, PRDM9, and FBXW7 and copy number variations in chromosomes 3, 5, 7, and 18. We also observed widespread ncRNA correlation to concurrent TP53 and chromosome 3p loss, a compelling predictor of poor prognosis in HNSCCs. Three selected ncRNAs were additionally associated with tumor stage, HPV status, and other clinical characteristics, and modulation of their expression in vitro reveals differential regulation of genes involved in epithelial-mesenchymal transition and apoptotic response. This comprehensive characterization of the HNSCC non-coding transcriptome introduces new layers of understanding for the disease, and nominates a novel panel of transcripts with potential utility as prognostic markers or therapeutic targets.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer worldwide, with an estimated 600,000 new cases annually and a 50% five-year mortality rate [1]
To enhance molecular knowledge of HNSCC and define a non-coding RNA landscape of the disease, we profiled the transcriptome-wide dysregulation of long non-coding RNA, microRNA, and PIWI-interacting RNA using RNAsequencing data from 422 HNSCC patients in The Cancer Genome Atlas (TCGA). 307 non-coding transcripts differentially expressed in HNSCC were significantly correlated with patient survival, and associated with mutations in TP53, CDKN2A, CASP8, PRDM9, and FBXW7 and copy number variations in chromosomes 3, 5, 7, and 18
To identify HNSCC-dysregulated non-coding RNA (ncRNA), we utilized all HNSCC tumor-paired adjacent normal RNA-sequencing data in TCGA on 15 June 2014. These data consisted of: (1) 40 tumor-normal RNA-seq datasets, for long non-coding RNA (lncRNA) profiling; and (2) 43 tumor-normal small RNA-seq datasets and Level 3 gene expression analyses, for PIWI-interacting RNA (piRNA) and miRNA profiling, respectively. ncRNA expression was obtained by alignment of sequencing datasets to custom gene annotations containing 113,438 lncRNA transcripts and 27,127 piRNAs, or extracted from corresponding TCGA Level 3 gene expression analyses profiling 1,046 miRNAs
Summary
HNSCC is the sixth leading cancer worldwide, with an estimated 600,000 new cases annually and a 50% five-year mortality rate [1]. Previous characterization of molecular features in HNSCC [2,3,4,5], with the aid of large-scale cancer genomics initiatives such as The Cancer Genome Atlas (TCGA) [6, 7], have generated important insights for stratifying HNSCCs and delineating tumor subtypes. These analyses, almost exclusively concentrated on the protein-coding genome, critically overlook alterations in the vast non-coding transcriptome that may substantially contribute to HNSCC pathogenesis and progression. The involvement of PIWIinteracting RNAs (piRNA) remains an even greater enigma, its dysregulation in breast, lung, and gastric cancers having only recently been uncovered [18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
