title: Treatment of obstructive sleep apnea alters cancer-associated transcriptional signatures in circulating leukocytes.
abstract: BACKGROUND
  Obstructive sleep apnea (OSA) has been associated with a number of chronic disorders that may improve with effective therapy. However, the molecular pathways affected by continuous positive airway pressure (CPAP) treatment are largely unknown. We sought to assess the system-wide consequences of CPAP therapy by transcriptionally profiling peripheral blood leukocytes (PBLs).
  
  
  METHODS
  Subjects in whom severe OSA was diagnosed were treated with CPAP, and whole-genome expression measurement of PBLs was performed at baseline and following therapy. We used gene set enrichment analysis (GSEA) to identify pathways that were differentially enriched. Network analysis was then applied to highlight key drivers of processes influenced by CPAP.
  
  
  RESULTS
  Eighteen subjects with significant OSA underwent CPAP therapy and microarray analysis of their PBLs. Treatment with CPAP improved apnea-hypopnea index (AHI), daytime sleepiness, and blood pressure, but did not affect anthropometric measures. GSEA revealed a number of enriched gene sets, many of which were involved in neoplastic processes and displayed downregulated expression patterns in response to CPAP. Network analysis identified several densely connected genes that are important modulators of cancer and tumor growth.
  
  
  CONCLUSIONS
  Effective therapy of OSA with CPAP is associated with alterations in circulating leukocyte gene expression. Functional enrichment and network analyses highlighted transcriptional suppression in cancer-related pathways, suggesting potentially novel mechanisms linking OSA with neoplastic signatures.
authors.affiliation: Computational Medicine Core, Center for Lung Biology ; UW Medicine Sleep Center, Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Sina A
authors.initials: SA
authors.lastname: Gharib
authors.affiliation: Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
authors.forename: Ashley N
authors.initials: AN
authors.lastname: Seiger
authors.affiliation: Digestive Disorders Institute.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Hayes
authors.affiliation: Sleep Disorders Center, Neurologic Institute, Cleveland Clinic Foundation, Cleveland, OH.
authors.forename: Reena
authors.initials: R
authors.lastname: Mehra
authors.affiliation: Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
authors.forename: Sanjay R
authors.initials: SR
authors.lastname: Patel
mesh_terms: D000886:Anthropometry; D001794:Blood Pressure / Q000502:physiology; D045422:Continuous Positive Airway Pressure; D005260:Female; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D007962:Leukocytes / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012890:Sleep / Q000502:physiology; D020181:Sleep Apnea, Obstructive / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D014158:Transcription, Genetic / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics
keywords: Microarray; cancer; network; sleep apnea; white blood cell