The non-coding landscape of head and neck squamous cell carcinoma

• DOI: 10.18632/oncotarget.9979
• Publication Date: 2016-06-14T00:21:37Z
• Authors: Angela E. Zou; Hao Zheng; Maarouf A. Saad; Mehran Rahimy; Jonjei Ku; Selena Z. Kuo; Thomas K. Honda; Jessica Wang-Rodr...; Yinan Xuan; Avinaash Korrapati; Vicky Yu; Pranav Singh; Jennifer R. Grandis; Charles C. King; Scott M. Lippman; Xiao Qi Wang; Andrew Hinton; Weg M. Ongkeko
• Keywords: Adult; Male; 0301 basic medicine; RNA, Untranslated; non-coding RNA; Oncology and Carcinogenesis; RNA-sequencing; 610; Cell Line; 03 medical and health sciences; Rare Diseases; cancer transcriptomics; Cell Line, Tumor; Genetics; 80 and over; Humans; Dental/Oral and Craniofacial Disease; Cancer; Aged; Aged, 80 and over; Neoplastic; Tumor; Sequence Analysis, RNA; Squamous Cell Carcinoma of Head and Neck; Gene Expression Profiling; Human Genome; Carcinoma; Untranslated; Middle Aged; 3. Good health; Gene Expression Regulation, Neoplastic; MicroRNAs; Good Health and Well Being; Squamous Cell; Gene Expression Regulation; Head and Neck Neoplasms; Carcinoma, Squamous Cell; RNA; Long Noncoding; head and neck cancer; Female; RNA, Long Noncoding; Transcriptome; Sequence Analysis; Biotechnology; Research Paper

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.