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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

  • Translational Research and Biomarkers
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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, BRAF V600E mutation, 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 BRAF V600E.

Conclusion

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.

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Disclosures

Jin Wook Yi, Su-jin Kim, Jong Kyu Kim, Chan Yong Seong, Hyeong Won Yu, Young Jun Chai, June Young Choi, and Kyu Eun Lee have no disclosures to declare.

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Authors and Affiliations

  1. Department of Surgery, Seoul National University Hospital and College of Medicine, Seoul, Korea

    Jin Wook Yi MD, Su-jin Kim MD, PhD, Jong Kyu Kim MD, Chan Yong Seong MD & Kyu Eun Lee MD, PhD

  2. Department of Surgery, Seoul National University Bundang Hospital and College of Medicine, Seongnam, Korea

    Hyeong Won Yu MD & June Young Choi MD

  3. Department of Surgery, Seoul National University Boramae Hospital, Seoul, Korea

    Young Jun Chai MD

Authors
  1. Jin Wook Yi MD
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  2. Su-jin Kim MD, PhD
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  3. Jong Kyu Kim MD
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  4. Chan Yong Seong MD
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  5. Hyeong Won Yu MD
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  6. Young Jun Chai MD
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  7. June Young Choi MD
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  8. Kyu Eun Lee MD, PhD
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Corresponding author

Correspondence to Su-jin Kim MD, PhD.

Electronic supplementary material

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Supplementary material 1 (DOCX 15 kb)

Supplementary material 2 (DOCX 25 kb)

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10434_2017_5780_MOESM6_ESM.tiff

Correlation plot between ESR1 mRNA and ER-α protein expression. (A) ESR1 mRNA versus ER-α-RV (B) ESR1 mRNA versus ER-α-pS118-RV. Supplementary material 6 (TIFF 1777 kb)

10434_2017_5780_MOESM7_ESM.tif

Overall survival in the lower and higher gene expression groups, as determined using the Kaplan–Meier method. (A) Survival difference according to ESR1 gene expression levels (B) Survival difference according to ESR ratio. Supplementary material 7 (TIFF 3770 kb)

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Yi, J.W., Kim, Sj., Kim, J.K. et al. 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. Ann Surg Oncol 24, 3754–3762 (2017). https://doi.org/10.1245/s10434-017-5780-z

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  • DOI: https://doi.org/10.1245/s10434-017-5780-z

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