Age-associated mortality is partially mediated by TERT promoter mutation status in differentiated thyroid carcinoma

• Published in: PloS one 2023-11, Vol.18 (11), p.e0294145-e0294145
• Main Authors: Heo, Jung, Lee, Sungjoo, Park, Jun, Yang, Heera, Park, Hyunju, Ki, Chang-Seok, Oh, Young Lyun, Kim, Hye In, Kim, Sun Wook, Chung, Jae Hoon, Kim, Kyunga, Kim, Tae Hyuk
• Format: Article
• Language: English
• Subjects: Ablation; Age; Aging; Biology and Life Sciences; Care and treatment; Diagnosis; Evaluation; Health aspects; Health care facilities; Iodine; Medical diagnosis; Medical prognosis; Medicine and Health Sciences; Metastasis; Mortality; Mutation; Patients; Physical Sciences; Regression models; Research and Analysis Methods; RNA-directed DNA polymerase; Survival analysis; Telomerase; Telomerase reverse transcriptase; Thyroid; Thyroid cancer; Thyroid carcinoma; Thyroidectomy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0294145

Age at diagnosis (AAD) and telomerase reverse transcriptase (TERT) promoter mutations are prognostic factors in differentiated thyroid carcinoma (DTC), and the prevalence of the mutations increases with AAD. Considering this correlation, we investigated whether an interaction between AAD and the mutations is present and whether the mutation mediates the effect of AAD on the mortality rate in DTC. The study included 393 patients with DTC who were followed-up after thyroidectomy at a single medical center in Korea from 1994 to 2004. Multivariable Cox regression was used to investigate the interaction of AAD and TERT promoter mutation. Mediation analysis was conducted using a regression-based causal mediation model. The age-associated mortality rate increased progressively in all DTC patients and wild-type TERT group (WT-TERT) with a linear trend (p < 0.001) contrary to mutant TERT group (M-TERT) (p = 0.301). Kaplan-Meier curves declined progressively with increasing AAD in the entire group, but the change was without significance in M-TERT. The effect of AAD on mortality was not significant (adjusted HR: 1.07, 95% CI 0.38-3.05) in M-TERT. An interaction between AAD and TERT promoter mutation (p = 0.005) was found in a multivariable Cox regression. TERT promoter mutations mediated the effect of AAD on the mortality rate by 36% in DTC in a mediation analysis. Considering the mediation of TERT promoter mutation on the effect of AAD on mortality, inclusion of TERT promoter mutation in a stage classification to achieve further individualized prediction in DTC is necessary.