title: Smoking status regulates a novel panel of PIWI-interacting RNAs in head and neck squamous cell carcinoma.
abstract: Smoking remains a primary etiological factor in head and neck squamous cell carcinoma (HNSCC). Given that non-coding RNAs (ncRNAs), including PIWI-interacting RNAs (piRNAs), have emerged as mediators of initiation and progression in head and neck malignancies, we undertook a global study of piRNA expression patterns in smoking-associated HNSCC.
  
  
  
  Using RNA-sequencing data from 256 current smoker and lifelong nonsmoker samples in The Cancer Genome Atlas (TCGA), we analyzed the differential expression patterns of 27,127 piRNAs across patient cohorts stratified by tobacco use, with HPV16 status and tumor status taken into account. We correlated their expression to clinical characteristics and to smoking-induced alterations of PIWI proteins, the functional counterparts of piRNAs. Finally, we correlated our identified piRNAs and PIWI proteins to known chromosomal aberrations in HNSCC to understand their wider-ranging genomic effects.
  
  
  
  Our analyses implicated a 13-member piRNA panel in smoking-related HNSCC, among which NONHSAT123636 and NONHSAT113708 associated with tumor stage, NONHSAT067200 with patient survival, and NONHSAT081250 with smoking-altered PIWIL1 protein expression. 6 piRNAs as well as PIWIL1 correlated with genomic alterations common to HNSCC, including TP53 mutation, TP53-3p co-occurrence, and 3q26, 8q24, and 11q13 amplification. Collectively, our findings provide novel insights into the etiology-specific piRNA landscape of smoking-induced HNSCC.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, United States. Electronic address: arkrishn@ucsd.edu.
authors.forename: Aswini R
authors.initials: AR
authors.lastname: Krishnan
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, United States. Electronic address: akorrapa@ucsd.edu.
authors.forename: Avinaash
authors.initials: A
authors.lastname: Korrapati
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, United States. Electronic address: azou@ucsd.edu.
authors.forename: Angela E
authors.initials: AE
authors.lastname: Zou
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, United States. Electronic address: yuq024@ucsd.edu.
authors.forename: Yuanhao
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China. Electronic address: xqwang@hku.hk.
authors.forename: Xiao Qi
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, United States. Electronic address: jcalifano@ucsd.edu.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
authors.affiliation: Veterans Administration Medical Center and Department of Pathology, University of California, San Diego, La Jolla, CA, United States. Electronic address: jessica.wang-rodriguez@va.gov.
authors.forename: Jessica
authors.initials: J
authors.lastname: Wang-Rodriguez
authors.affiliation: Department of Medicine and Moores Cancer Center, University of California, San Diego, La Jolla, CA, United States. Electronic address: slippman@ucsd.edu.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.affiliation: Graduate School of Public Health, San Diego State University, San Diego, CA, United States. Electronic address: mhovell@cbeachsdsu.org.
authors.forename: Melbourne F
authors.initials: MF
authors.lastname: Hovell
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of California, San Diego, La Jolla, CA, United States. Electronic address: wongkeko@ucsd.edu.
authors.forename: Weg M
authors.initials: WM
authors.lastname: Ongkeko
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008297:Male; D034741:RNA, Small Interfering / Q000378:metabolism*; D012907:Smoking; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D034741:RNA, Small Interfering
keywords: Head and neck neoplasms; RNA; Small interfering; Smoking