title: Upregulation of the ESR1 Gene and ESR Ratio (ESR1/ESR2) is Associated with a Worse Prognosis in Papillary Thyroid Carcinoma: The Impact of the Estrogen Receptor α/β Expression on Clinical Outcomes in Papillary Thyroid Carcinoma Patients.
abstract: BACKGROUND
  A gender disparity exists with respect to the incidence of papillary thyroid cancer (PTC), suggesting that sex hormones such as estrogen play a role in PTC development and progression. In this study, we compared estrogen receptor gene expression patterns in PTCs to determine the clinical significance of estrogen gene expression in PTC.
  
  
  METHODS
  We analyzed ESR1 and ESR2 messenger RNA expression counts using data from The Cancer Genome Atlas (TCGA). To validate the results of TCGA analysis, we analyzed microarray data (GSE 54958) from the Gene Expression Omnibus.
  
  
  RESULTS
  ESR1 gene expression and ESR ratio (ESR1/ESR2) were significantly higher in PTC tissues than in paired normal thyroid tissues (mean 659.427 vs. 264.045 for ESR1, 92.017 vs. 19.064 for ESR ratio). Among female patients, ESR1 expression and ESR ratio were negatively correlated with increased age. ESR1 expression and ESR ratio were higher in patients with classic PTC, lymphovascular invasion, BRAFV600Emutation, and radioiodine therapy. Classification analysis demonstrated that higher ESR1 expression and a higher ESR ratio faced a worse overall survival (hazard ratio 6.348 for ESR1, 4.031 for ESR ratio). Validation microarray analysis demonstrated that ESR1 expression and ESR ratio were higher in tumor tissues, classic PTC, and BRAFV600E.
  
  
  CONCLUSIONS
  Higher ESR1 expression and a higher ESR ratio were associated with aggressive prognostic factors and worse overall survival in female PTC patients. Our results suggest that ESR1 and ESR ratio can be used as prognostic markers to predict female patient survival and have potential as a therapeutic target.
authors.affiliation: Department of Surgery, Seoul National University Hospital and College of Medicine, Seoul, Korea.
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Yi
authors.affiliation: Department of Surgery, Seoul National University Hospital and College of Medicine, Seoul, Korea. su.jin.kim.md@gmail.com.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Surgery, Seoul National University Hospital and College of Medicine, Seoul, Korea.
authors.forename: Jong Kyu
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Surgery, Seoul National University Hospital and College of Medicine, Seoul, Korea.
authors.forename: Chan Yong
authors.initials: CY
authors.lastname: Seong
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital and College of Medicine, Seongnam, Korea.
authors.forename: Hyeong Won
authors.initials: HW
authors.lastname: Yu
authors.affiliation: Department of Surgery, Seoul National University Boramae Hospital, Seoul, Korea.
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Chai
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital and College of Medicine, Seongnam, Korea.
authors.forename: June Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Surgery, Seoul National University Hospital and College of Medicine, Seoul, Korea.
authors.forename: Kyu Eun
authors.initials: KE
authors.lastname: Lee
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta