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Objectives.Thyroid cancer is the most common endocrine tumor, with rapidly increasing incidence worldwide. However, its transcriptomic characteristics associated with immunological signatures, driver fusion, and recurrence markers are still unclear. We aimed to investigate the transcriptomic characteristics of advanced papillary thyroid cancer patients.MethodsThis study included 282 papillary thyroid cancer tumor samples, and 155 normal samples from Chungnam National University Hospital and Seoul National University Hospital. Transcriptomic quantification was determined by high-throughput RNA sequencing. We investigated the association of clinical parameters and molecular signatures using RNA sequencing. We validated the predictive biomarker using The Cancer Genome Atlas (TCGA) database.ResultsBy comparing differentially expressed genes, gene sets, and pathways in papillary thyroid cancer than normal adjacent of tumor tissue, we found increased immune signaling associated with cytokine or T-cell and decreased thyroid hormone synthetic pathways. In addition, patients with recurrence represented increased CD8+ T-cell signature and Th1 cells signature, respectively. Interestingly, we found differentially overexpressed genes related to immune-escape signaling such as CTLA4, IDO1, LAG3, and PDCD1 in advanced PTC with low thyroid differentiation score (TDS). Fusion analysis showed that the PI3K and MAPK signaling pathways were regulated differently according to RET fusion partner genes (CCDC6 and NCOA4). Finally, we identified HOXD9 as a novel molecular biomarker that predicts the recurrence of thyroid cancer in addition to known risk factors (tumor size, lymph node metastasis, and extrathyroidal extension).ConclusionWe identified a high association with immune-escape signaling in the immune-hot group with aggressive clinical factors of Korean thyroid cancer patients. Moreover, RET fusion differentially regulated PI3K and MAPK signaling depending on the partner gene of RET, and HOXD9 was found to be a recurrence marker for advanced PTC patients.

Background: Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate-and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. Methods: This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The followup period is 5 years. Conclusion:The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.