title: Molecular pathways associated with mortality in papillary thyroid cancer.
abstract: BACKGROUND
  A better understanding of the molecular mechanisms involved in papillary thyroid cancer (PTC)-associated adverse outcome is needed to manage these patients effectively. Our objectives were to identify molecular pathways associated with unfavorable features and outcomes in patients with PTC.
  
  
  METHODS
  We performed genome-wide expression (GWE) analysis in 64 human tissue samples affected by PTC. Clinical, pathologic, and microarray data were analyzed to identify differentially expressed genes and pathways associated with unfavorable outcomes. Gene set enrichment analysis (GSEA) was used to determine which molecular pathways are associated with mortality.
  
  
  RESULTS
  GWE analysis identified 43, 115, and 40 genes that were significantly differentially expressed by gender, tumor differentiation status, and mortality, respectively, with a false-discovery rate of <5%. For mortality, GSEA revealed 7 enriched pathways, including transfer RNA synthesis, mitochondria and oxidative phosphorylation, porphyrin and chlorophyll metabolism, and fatty acid synthesis. Leading-edge analysis showed that 341 genes were significantly involved in the enriched pathways. Cluster analysis using 100 differentially expressed genes showed complete separation of patients by mortality.
  
  
  CONCLUSIONS
  To our knowledge, this is the first GWE analysis of PTC and adverse outcomes. We found 11 molecular pathways that were significantly associated with mortality resulting from PTC. A 100-gene signature completely separates patients with and without PTC-associated mortality.
authors.affiliation: Endocrine Oncology Section, Surgery Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA. niluboln@mail.nih.gov
authors.forename: Naris
authors.initials: N
authors.lastname: Nilubol
authors.forename: Chotiya
authors.initials: C
authors.lastname: Sukchotrat
authors.forename: Lisa
authors.initials: L
authors.lastname: Zhang
authors.forename: Mei
authors.initials: M
authors.lastname: He
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma; D002291:Carcinoma, Papillary; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012737:Sex Factors; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000401:mortality; D055815:Young Adult