The non-coding landscape of head and neck squamous cell carcinoma.
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.
Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California, United States of America.
Angela E
AE
Zou
Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California, United States of America.
Hao
H
Zheng
Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California, United States of America.
Maarouf A
MA
Saad
Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California, United States of America.
Mehran
M
Rahimy
Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California, United States of America.
Jonjei
J
Ku
Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California, United States of America.
Selena Z
SZ
Kuo
Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California, United States of America.
Thomas K
TK
Honda
Veterans Administration Medical Center and Department of Pathology, University of California San Diego, La Jolla, California, United States of America.
Jessica
J
Wang-Rodriguez
Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California, United States of America.
Yinan
Y
Xuan
Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California, United States of America.
Avinaash
A
Korrapati
Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California, United States of America.
Vicky
V
Yu
Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California, United States of America.
Pranav
P
Singh
Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, California, United States of America.
Jennifer R
JR
Grandis
Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America.
Charles C
CC
King
Department of Medicine and Moores Cancer Center, University of California San Diego, La Jolla, California, United States of America.
Scott M
SM
Lippman
Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China.
Xiao Qi
XQ
Wang
Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America.
Andrew
A
Hinton
Department of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California, United States of America.
Weg M
WM
Ongkeko
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D062085:RNA, Long Noncoding / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics*; D017423:Sequence Analysis, RNA; D000077195:Squamous Cell Carcinoma of Head and Neck; D059467:Transcriptome
D035683:MicroRNAs; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated
RNA-sequencing; cancer transcriptomics; head and neck cancer; non-coding RNA