Changes of biochemical factors and the effect on recurrence of medullary thyroid carcinoma after surgery.

Objective: Medullary thyroid carcinoma (MTC) is a rare malignancy secreting calcitonin (Ctn). We aimed to analyze the relationship between Ctn levels at different time points in patients with MTC, and evaluate its predictive effect on recurrence. Methods: A retrospective study of patients diagnosed with MTC in a large medical center were conducted in northern China. The interrelationships between preoperative Ctn, normalization of postoperative serum Ctn at the first month (NPS), and long-term biochemical cure as well as their predicting roles on structural recurrence were assessed. Results: A total of 212 patients were included in this study. The median follow-up time was 59.5 months. The 5- and 10-year cumulative disease-free survival rates were 81.5 % and 66.8 %, respectively. NPS (OR: 216.33, 95 % CI: 28.69-1631.09, P < 0.001) and absence of structural recurrence (OR: 61.71, 95 % CI: 3.90-975.31; P = 0.003) were associated with biochemical cure. Non-biochemical cure (OR: 28.76; 95 % CI: 2.84-290.86; P = 0.004, HR: 14.63, 95 % CI: 2.27-94.07, P = 0.005), larger tumor size (OR: 8.79, 95 % CI: 2.12-36.40, P = 0.003, HR: 5.41, 95 % CI: 2.04-14.37, P = 0.001), and multifocality (OR: 4.02, 95 % CI: 1.06-15.17, P = 0.040, HR: 3.00, 95 % CI: 1.18-7.60, P = 0.021) were unfavorable independent predictors of structural recurrence and disease-free survival. For sporadic MTC confined to the thyroid lobe, there was no difference in biochemical or structural prognosis between the different surgeries in the subgroup analysis. Conclusions: NPS, rather than preoperative Ctn, predicted long-term biochemical cure for MTC. Non-biochemical cure, larger tumor burden including larger tumor size and multifocality at initial surgery, served as worse prognostic predictors.

Multidimensional data analysis revealed thyroiditis-associated TCF19 SNP rs2073724 as a highly ranked protective variant in thyroid cancer.

BACKGROUND: Thyroid cancer represents the most prevalent malignant endocrine tumour, with rising incidence worldwide and high mortality rates among patients exhibiting dedifferentiation and metastasis. Effective biomarkers and therapeutic interventions are warranted in aggressive thyroid malignancies. The transcription factor 19 (TCF19) gene has been implicated in conferring a malignant phenotype in cancers. However, its contribution to thyroid neoplasms remains unclear. RESULTS: In this study, we performed genome-wide and phenome-wide association studies to identify a potential causal relationship between TCF19 and thyroid cancer. Our analyses revealed significant associations between TCF19 and various autoimmune diseases and human cancers, including cervical cancer and autoimmune thyroiditis, with a particularly robust signal for the deleterious missense variation rs2073724 that is associated with thyroid function, hypothyroidism, and autoimmunity. Furthermore, functional assays and transcriptional profiling in thyroid cancer cells demonstrated that TCF19 regulates important biological processes, especially inflammatory and immune responses. We demonstrated that TCF19 could promote the progression of thyroid cancer in vitro and in vivo and the C>T variant of rs2073724 disrupted TCF19 protein binding to target gene promoters and their expression, thus reversing the effect of TCF19 protein. CONCLUSIONS: Taken together, these findings implicate TCF19 as a promising therapeutic target in aggressive thyroid malignancies and designate rs2073724 as a causal biomarker warranting further investigation in thyroid cancer.

SETMAR Facilitates the Differentiation of Thyroid Cancer by Regulating SMARCA2-Mediated Chromatin Remodeling.

Thyroid cancer is the most common type of endocrine cancer, and most patients have a good prognosis. However, the thyroid cancer differentiation status strongly affects patient response to conventional treatment and prognosis. Therefore, exploring the molecular mechanisms that influence the differentiation of thyroid cancer is very important for understanding the progression of this disease and improving therapeutic options. In this study, SETMAR as a key gene that affects thyroid cancer differentiation is identified. SETMAR significantly regulates the proliferation, epithelial-mesenchymal transformation (EMT), thyroid differentiation-related gene expression, radioactive iodine uptake, and sensitivity to MAPK inhibitor-based redifferentiation therapies of thyroid cancer cells. Mechanistically, SETMAR methylates dimethylated H3K36 in the SMARCA2 promoter region to promote SMARCA2 transcription. SMARCA2 can bind to enhancers of the thyroid differentiation transcription factors (TTFs) PAX8, and FOXE1 to promote their expression by enhancing chromatin accessibility. Moreover, METTL3-mediated m6A methylation of SETAMR mRNA is observed and showed that this medication can affect SETMAR expression in an IGF2BP3-dependent manner. Finally, the METTL3-14-WTAP activator effectively facilitates the redifferentiation of thyroid cancer cells via the SETMAR-SMARCA2-TTF axis utilized. The research provides novel insights into the molecular mechanisms underlying thyroid cancer dedifferentiation and provides a new approach for therapeutically promoting redifferentiation.