Endocrinol Metab.  2023 Dec;38(6):720-729. 10.3803/EnM.2023.1758.

Comparative Analysis of Driver Mutations and Transcriptomes in Papillary Thyroid Cancer by Region of Residence in South Korea

• Lee J
• Jeong S
• Lee HY
• Park S
• Jeong M
• Jo YS

• KMID: 2549265
• DOI: http://doi.org/10.3803/EnM.2023.1758

Abstract

Background
Radiation exposure is a well-known risk factor for papillary thyroid cancer (PTC). South Korea has 24 nuclear reactors in operation; however, no molecular biological analysis has been performed on patients with PTC living near nuclear power plants.
Methods
We retrospectively included patients with PTC (n=512) divided into three groups according to their place of residence at the time of operation: inland areas (n=300), coastal areas far from nuclear power plants (n=134), and nuclear power plant areas (n=78). After propensity score matching (1:1:1) by age, sex, and surgical procedure, the frequency of representative driver mutations and gene expression profiles were compared (n=50 per group). Epithelial-mesenchymal transition (EMT), BRAF, thyroid differentiation, and radiation scores were calculated and compared.
Results
No significant difference was observed in clinicopathological characteristics, including radiation exposure history and the frequency of incidentally discovered thyroid cancer, among the three groups. BRAF^V600E mutation was most frequently detected in the groups, with no difference among the three groups. Furthermore, gene expression profiles showed no statistically significant difference. EMT and BRAF scores were higher in our cohort than in cohorts from Chernobyl tissue bank and The Cancer Genome Atlas Thyroid Cancer; however, there was no difference according to the place of residence. Radiation scores were highest in the Chernobyl tissue bank but exhibited no difference according to the place of residence.
Conclusion
Differences in clinicopathological characteristics, frequency of representative driver mutations, and gene expression profiles were not observed according to patients’ region of residence in South Korea.

Keyword

Thyroid cancer, papillary; Radiation genomics; Transcriptome; Geographic locations; Nuclear power plants

Figure

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  Fig. 1. Dot plot for the gene set enrichment analysis (GSEA) results according to patients’ residential area (n=50 per group). GSEA presents gene sets enriched in the patient cohort in inland areas compared with that in coastal areas (A), patient cohort in coastal areas compared with that in inland areas (B), patient cohort in inland areas compared with that in areas near nuclear power plants (NPPs) (C), patient cohort in areas near NPPs compared with that in inland areas (D), patient cohort in coastal areas compared with that in areas near NPPs (E), and patient cohort in areas near NPPs compared with that in coastal areas (F). G2M, gap 2 mitosis; PI3K, phosphoinositide 3-kinase; mTOR, mammalian target of rapamycin; UV, ultraviolet; DN, down; TGF, transforming growth factor; E2F, E2F transcription factor; TNFA, tumor necrosis factor alpha; NFKB, nuclear factor kappa-light-chain-enhancer of activated B cells; FDR, false discovery rate.

• 

  Fig. 2. Comparisons of signature gene scores among our cohort, the Chernobyl tissue bank, and The Cancer Genome Atlas Thyroid Cancer (TCGA THCA). Scores representing the expression status of genes associated with epithelial-mesenchymal transition (A), BRAF (B), thyroid differentiation (C), and radiation exposure (D). Group comparisons were performed using Mann-Whitney U test and Student t test accordingly. Error bars are presented with standard errors of the mean. NPP, nuclear power plant. aP<0.05; bP<0.01.

• 

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