Faculty, Staff and Student Publications
Publication Date
1-21-2025
Journal
The Journal of Clinical Endocrinology and Metabolism
Abstract
Context: Thyroid differentiation score (TDS), calculated based on mRNA expression levels of 16 genes controlling thyroid metabolism and function, has been proposed as a measure to quantify differentiation in papillary thyroid carcinoma (PTC).
Objective: The objective of this study is to determine whether TDS is associated with survival outcomes across patient cohorts.
Methods: Two independent cohorts of patients with PTC were used: (1) The Cancer Genome Atlas (TCGA) thyroid cancer study (N = 372), (2) MD Anderson Cancer Center (MDACC) cohort (N = 111). The primary survival outcome of interest was progression-free interval (PFI). Association with overall survival (OS) was also explored. The Kaplan-Meier method and Cox proportional hazards models were used for survival analyses.
Results: In both cohorts, TDS was associated with tumor and nodal stage at diagnosis as well as tumor driver mutation status. High TDS was associated with longer PFI on univariable analyses across cohorts. After adjusting for overall stage, TDS remained significantly associated with PFI in the MDACC cohort only (adjusted hazard ratio [aHR] 0.67, 95% CI 0.52-0.85). In subgroup analyses stratified by tumor driver mutation status, higher TDS was most consistently associated with longer PFI in BRAFV600E-mutated tumors in the MDACC cohort after adjusting for overall stage (TCGA: aHR 0.60, 95% CI 0.33-1.07; MDACC: aHR 0.59, 95% CI 0.42-0.82). For OS, increasing TDS was associated with longer OS in the overall MDACC cohort (aHR = 0.78, 95% CI 0.63-0.96), where the median duration of follow-up was 12.9 years.
Conclusion: TDS quantifies the spectrum of differentiation status in PTC and may serve as a potential prognostic biomarker in PTC, mostly promisingly in BRAFV600E-mutated tumors.
Keywords
Humans, Thyroid Neoplasms, Female, Male, Thyroid Cancer, Papillary, Middle Aged, Prognosis, Cell Differentiation, Adult, Thyroid Gland, Biomarkers, Tumor, Aged, Mutation, Cohort Studies, Follow-Up Studies, Survival Rate, Kaplan-Meier Estimate, papillary thyroid carcinoma, biomarker, survival outcomes, differentiation
DOI
10.1210/clinem/dgae532
PMID
39087944
PMCID
PMC11747754
PubMedCentral® Posted Date
8-1-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons