EP1024TSHR promoter methylation level changes as a prognostic blood-based biomarker in follicular thyroid carcinoma

Abstract

Introduction Papillary thyroid carcinoma (PTC) is the most common type of differentiated thyroid cancer, accounting for about 80% of all cases of thyroid cancer. Generally, PTC is an indolent disease and shows a good prognosis in most patients. However, up to 30% of patients have local tumor renewal or systemic spread. It is crucial to identify patients with a high risk of disease progression. DNA methylation biomarkers may provide clinically valuable information and improve the early non-invasive prognosis of PTC. Aim of the study To evaluate DNA methylation level changes of selected genes in peripheral blood plasma samples in PTC patients before and 4-6 weeks after surgery. Methods The studyincluded 68 patients with a histologically confirmed diagnosis of PTC with different histological variants: classical (nZ 29), diffuse sclerosing (nZ 17), follicular (nZ 18), and tall cell carcinoma (nZ 4). Peripheral blood samples were collected before surgery and 4-6 weeks after surgery during 2020 – 2021 in Hospital of Lithuanian University of Health Sciences, Kaunas clinics. DNA methylation level changes of TSHR gene were analysed by quantitative methylation-sensitive polymerase chain reaction. DNA methylation levels of TSHR were compared before and one month after the surgery using both paired and non-paired non-parametrical tests. Results Significantly lower TSHR promoter methylation levels were found 4-6 weeks after surgery compared to samples collected before surgery (PZ0.034) in follicular variant of PTC. Paired sample analysis showed a statistically higher TSHR methylation level before surgery compared to TSHR methylation level after surgery in follicular variant PTC (PZ0.002). Conclusion TSHR promoter methylation level changes may be a promising biomarker in predicting PTC prognosis. Funding This study was supported by the Lithuanian Research Council (Grant No. S-SEN20-14 “The role of epigenetic markers for early detection of papillary thyroid carcinoma and prognostic significance in long-term outcome in elderly patients”)