The non-coding landscape of head and neck squamous cell carcinoma
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Angela E. Zou1, Hao Zheng1, Maarouf A. Saad1, Mehran Rahimy1, Jonjei Ku1, Selena Z. Kuo1, Thomas K. Honda1, Jessica Wang-Rodriguez2, Yinan Xuan1, Avinaash Korrapati1, Vicky Yu1, Pranav Singh1, Jennifer R. Grandis3, Charles C. King4, Scott M. Lippman5, Xiao Qi Wang6, Andrew Hinton4,*, Weg M. Ongkeko1,*
1Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California, United States of America
2Veterans Administration Medical Center and Department of Pathology, University of California San Diego, La Jolla, California, United States of America
3Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, California, United States of America
4Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America
5Department of Medicine and Moores Cancer Center, University of California San Diego, La Jolla, California, United States of America
6Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China
Weg M. Ongkeko, email: [email protected]
Keywords: head and neck cancer, non-coding RNA, RNA-sequencing, cancer transcriptomics
Received: March 19, 2016 Accepted: May 05, 2016 Published: June 13, 2016
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.
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