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Smoking status regulates a novel panel of PIWI-interacting RNAs in head and neck squamous cell carcinoma.

ABSTRACT: OBJECTIVE: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. MATERIALS AND METHODS: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. RESULTS AND CONCLUSION: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.

SUBMITTER: Krishnan AR

PROVIDER: S-EPMC5291169 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Smoking status regulates a novel panel of PIWI-interacting RNAs in head and neck squamous cell carcinoma.

Krishnan Aswini R AR Korrapati Avinaash A Zou Angela E AE Qu Yuanhao Y Wang Xiao Qi XQ Califano Joseph A JA Wang-Rodriguez Jessica J Lippman Scott M SM Hovell Melbourne F MF Ongkeko Weg M WM

Oral oncology 20161231

<h4>Objective</h4>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.<h4>Materials and methods</h4>Using RNA-sequencing data from 256 current smoker and lifelong nonsmoker samples in The Cancer Genome Atla ...[more]

PMID: 28109471

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Project description:Importance:While the adverse association between smoking and head and neck squamous cell carcinoma (HNSCC) survival has been well described, there are also inconclusive studies and those that report no significant changes in HNSCC survival and overall mortality due to smoking. There is also a lack of studies investigating the association of marital status on smoking status at diagnosis for patients with HNSCC. Objective:To examine the association between patient smoking status at HNSCC diagnosis and survival and the association between marital status and smoking in these patients. Design, Setting, and Participants:This retrospective cohort study was conducted by querying the Saint Louis University Hospital Tumor Registry for adults with a diagnosis of HNSCC and treated at the university academic medical center between 1997 and 2012; 463 confirmed cases were analyzed. Main Outcomes and Measures:Cox proportional hazards regression analysis was used to evaluate association of survival with smoking status at diagnosis and covariates. A multivariate logistic regression model was used to assess whether marital status was associated with smoking at diagnosis adjusting for covariates. Results:Of the 463 total patients (338 men, 125 women), 92 (19.9%) were aged 18 to 49 years; 233 (50.3%) were aged 50 to 65 years; and 138 (29.8%) were older than 65 years. Overall, 56.2% of patients were smokers at diagnosis (n?=?260); 49.6% were married (n?=?228); and the mortality rate was 54.9% (254 died). A majority of patients were white (81.0%; n?=?375). Smokers at diagnosis were more likely to be younger (ie, <65 years), unmarried, and to drink alcohol. We found a statistically significant difference in median survival time between smokers (89 months; 95% CI, 65-123 months) and nonsmokers at diagnosis (208 months; 95% CI, 129-235 months). In the adjusted Cox proportional hazards model, patients who were smokers at diagnosis were almost twice as likely to die during the study period as nonsmokers (hazard ratio, 1.98; 95% CI, 1.42-2.77). In the multivariate logistic regression analysis, unmarried patients were 76% more likely to use tobacco than married patients (adjusted odds ratio, 1.76; 95% CI, 1.08-2.84). Conclusions and Relevance:Smokers were almost twice as likely as nonsmokers to die during the study period. We also found that those who were married were less likely to be smokers at diagnosis. Our study suggests that individualized cancer care should incorporate social support and management of cancer risk behaviors.

Dataset Information

Smoking status regulates a novel panel of PIWI-interacting RNAs in head and neck squamous cell carcinoma.

Publications

Smoking status regulates a novel panel of PIWI-interacting RNAs in head and neck squamous cell carcinoma.

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