Isolated TERT promoter mutation may define a high-risk prognostic subgroup in papillary thyroid carcinoma: an exploratory, hypothesis-generating analysis of TCGA and GSE33630 datasets
- 1Department of Pathology, Suzhou BenQ Medical Center
Abstract
Background: The prognostic value of combined BRAF V600E and TERT promoter (TERTp) mutations in papillary thyroid carcinoma (PTC) has been established in surgical cohorts. However, the independent impact of TERTp mutation in the absence of BRAF mutation remains underexplored, particularly within publicly available genomic datasets.
Methods: We analyzed 49 PTC patients with available BRAF and TERTp mutation data from The Cancer Genome Atlas (TCGA) Thyroid Carcinoma (THCA) cohort. Patients were stratified into four subgroups: BRAF−/TERTp−, BRAF+/TERTp−, BRAF−/TERTp+, and BRAF+/TERTp+. Progression-free interval (PFI) was compared using Kaplan–Meier analysis and Cox proportional hazards regression. Additionally, differential gene expression analysis was performed using GSE33630 (n = 42 PTC samples) to explore transcriptomic correlates of BRAF mutation.
Results: Overall log-rank analysis revealed significant PFI differences across the four subgroups (p < 0.001). The BRAF−/TERTp+ group demonstrated the worst prognosis, with 3 of 5 patients experiencing disease progression (median PFI = 5.7 months), compared with no events in the BRAF−/TERTp− group. Univariable Cox regression identified BRAF−/TERTp+ as the strongest adverse predictor (HR = 9.57, 95% CI: 2.02–45.25, p = 0.004), which remained significant after adjustment for age (HR = 8.38, 95% CI: 1.67–42.19, p = 0.010). In GSE33630, 42 differentially expressed genes (DEGs; FDR < 0.05) were identified between BRAF-mutant and wild-type PTC, including downregulation of PCDH20, HES1, and TLR2, and upregulation of DAPK2.
Conclusions: This hypothesis-generating, exploratory analysis suggests that isolated TERTp mutation may represent an underrecognized high-risk PTC subgroup. The wide confidence intervals reflect the small sample size and limited event counts inherent to this dataset. These preliminary findings warrant validation in larger prospective cohorts with comprehensive molecular annotation.
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BibTeX
@article{guan2026isolated,
title = {{Isolated TERT promoter mutation may define a high-risk prognostic subgroup in papillary thyroid carcinoma: an exploratory, hypothesis-generating analysis of TCGA and GSE33630 datasets}},
author = {Bing Guan and Rong Zhou and Sijia Zhang and Yawen Chen and Lulu Li and Ping He},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1881969},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1881969/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Isolated TERT promoter mutation may define a high-risk prognostic subgroup in papillary thyroid carcinoma: an exploratory, hypothesis-generating analysis of TCGA and GSE33630 datasets
AU - Bing Guan
AU - Rong Zhou
AU - Sijia Zhang
AU - Yawen Chen
AU - Lulu Li
AU - Ping He
PY - 2026
DA - 2026/10/15
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1881969
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1881969/full
AB - Background: The prognostic value of combined BRAF V600E and TERT promoter (TERTp) mutations in papillary thyroid carcinoma (PTC) has been established in surgical cohorts. However, the independent impact of TERTp mutation in the absence of BRAF mutation remains underexplored, particularly within publicly available genomic datasets. Methods: We analyzed 49 PTC patients with available BRAF and TERTp mutation data from The Cancer Genome Atlas (TCGA) Thyroid Carcinoma (THCA) cohort. Patients were stratified into four subgroups: BRAF−/TERTp−, BRAF+/TERTp−, BRAF−/TERTp+, and BRAF+/TERTp+. Progression-free interval (PFI) was compared using Kaplan–Meier analysis and Cox proportional hazards regression. Additionally, differential gene expression analysis was performed using GSE33630 (n = 42 PTC samples) to explore transcriptomic correlates of BRAF mutation. Results: Overall log-rank analysis revealed significant PFI differences across the four subgroups (p < 0.001). The BRAF−/TERTp+ group demonstrated the worst prognosis, with 3 of 5 patients experiencing disease progression (median PFI = 5.7 months), compared with no events in the BRAF−/TERTp− group. Univariable Cox regression identified BRAF−/TERTp+ as the strongest adverse predictor (HR = 9.57, 95% CI: 2.02–45.25, p = 0.004), which remained significant after adjustment for age (HR = 8.38, 95% CI: 1.67–42.19, p = 0.010). In GSE33630, 42 differentially expressed genes (DEGs; FDR < 0.05) were identified between BRAF-mutant and wild-type PTC, including downregulation of PCDH20, HES1, and TLR2, and upregulation of DAPK2. Conclusions: This hypothesis-generating, exploratory analysis suggests that isolated TERTp mutation may represent an underrecognized high-risk PTC subgroup. The wide confidence intervals reflect the small sample size and limited event counts inherent to this dataset. These preliminary findings warrant validation in larger prospective cohorts with comprehensive molecular annotation.
SN - 1664-2392
ER -