title: Recurrence-associated genes in papillary thyroid cancer: An analysis of data from The Cancer Genome Atlas.
abstract: Recurrence of papillary thyroid cancer is not uncommon, but incorporating clinicopathologic parameters to predict recurrence is suboptimal. The aim of this study was to identify systemically recurrence-associated genes using The Cancer Genome Atlas RNA sequencing database.
  
  
  
  A total of 504 patients with transcriptome sequencing data of the primary neoplasm were included in this study. High and low levels of expression of each gene were defined by median splits. Differences in recurrence-free survival were compared using Kaplan-Meier curves and log-rank tests. Recurrence-associated genes were subjected to functional enrichment analyses with Kyoto Encyclopedia of Genes and Genomes annotation databases and Ingenuity Pathway Analysis.
  
  
  
  We found that 1,807 genes were associated with recurrence-free survival. There were 676 genes of which high expression was associated with a greater risk of recurrence. These genes were enriched in pathways involved in cell cycle regulation and DNA repair. Among 1,131 genes of which low expression was associated with recurrence, Kyoto Encyclopedia of Genes and Genomes-annotated functions were metabolism, calcium signaling, glycan biosynthesis, and the Notch signaling pathway. Canonical pathways identified by Ingenuity Pathway Analysis included RXR function, nitric oxide signaling, interleukin-8 signaling, and nutrient sensing. In addition, low expression of the majority of thyroid differentiation genes was associated with a significantly less recurrence-free survival.
  
  
  
  Upregulation of cell cycle-regulating and DNA repair genes appears to have a negative impact on recurrence-free survival in patients with papillary thyroid cancer. Furthermore, recurrence is associated with thyroid dedifferentiation.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan.
authors.forename: Ming-Nan
authors.initials: MN
authors.lastname: Chien
authors.affiliation: Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan; Graduate Institute of Medical Sciences and Department of Pharmacology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Po-Sheng
authors.initials: PS
authors.lastname: Yang
authors.affiliation: Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan; Graduate Institute of Medical Sciences and Department of Pharmacology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jie-Jen
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Department of Pathology, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan.
authors.forename: Tao-Yeuan
authors.initials: TY
authors.lastname: Wang
authors.affiliation: Department of Biomedical Sciences and Engineering, National Central University, Taoyuan City, Taiwan; Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
authors.forename: Yi-Chiung
authors.initials: YC
authors.lastname: Hsu
authors.affiliation: Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan; Graduate Institute of Medical Sciences and Department of Pharmacology, Taipei Medical University, Taipei, Taiwan. Electronic address: surg.mmh@gmail.com.
authors.forename: Shih-Ping
authors.initials: SP
authors.lastname: Cheng
mesh_terms: D000368:Aged; D015331:Cohort Studies; D004260:DNA Repair / Q000235:genetics*; D016208:Databases, Factual; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D016045:Human Genome Project; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D015398:Signal Transduction / Q000235:genetics; D016019:Survival Analysis; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D013965:Thyroidectomy / Q000009:adverse effects / Q000379:methods*