Objective: This study examined the effect of Sirtuin 4 (Sirt4), a NAD+-dependent deacetylase, on the proliferation and progression of papillary thyroid carcinoma (PTC).

Methods: Data from The Cancer Genome Atlas (TCGA) were analyzed to identify Sirt4 expression in thyroid cancer. Subsequently, the correlation between Sirt4 expression and clinical characteristics was examined in 205 PTC tissue samples. In vitro assays using three human thyroid cancer cell lines (B-CPAP, TPC-1, and SNU-790) were conducted to assess the effects of regulated Sirt4 expression on cell growth, apoptosis, invasion, and migration. Furthermore, in vivo experiments were performed in a xenograft mouse model.

Results: GEO and TCGA data indicated that Sirt4 expression is lower in thyroid cancer and Sirt4 downregulation is associated with poor overall survival. In our PTC tissues, positive Sirt4 expression was associated with decreased extracapsular extension. In in vitro experiments using three human thyroid cancer cell lines, overexpression of Sirt4 decreased cell survival, clonogenic potential, and invasion and migratory capabilities, as well as inducing apoptosis and increasing reactive oxygen species levels. Sirt4 overexpression upregulated E-cadherin and downregulated N-cadherin, suggesting its potential involvement in the regulation of epithelial–mesenchymal transition. These findings were confirmed in vivo using a xenograft mouse model.

Conclusion: This study provides novel insight into the potential contribution of Sirt4 to regulation of the pathological progression of PTC. The data suggest that Sirt4 plays a tumor-suppressive role in PTC by inhibiting growth, survival, and invasive potential. Future research should investigate the molecular mechanisms underlying these effects of Sirt4.

Objective: Previous reports suggest that a high body mass index (BMI) increases the risk of thyroid carcinoma. However, it remains unclear whether a high BMI is associated with the risk of BRAFV600E mutation. We aimed to assess whether a high BMI is associated with an increased risk of BRAFV600E mutation.

Design and Methods: We screened 6,558 PTC patients who had undergone BRAFV600E mutation testing between January 2009 and December 2017. After exclusion, 6,438 PTC patients were enrolled. We used logistic regression, and restricted cubic spline plots of the adjusted odd ratios (ORs) were illustrated to model the relationship between BMI and BRAFV600E mutation.

Results: Among the 6,438 patients, 5,102 (79.2%) had the BRAFV600E mutation, and 4,954 (76.9%) were female. The median BMI was 23.8 (21.6 – 26.2) kg/m2. The primary tumor size was ≤ 1cm in 4,226 patients (65.6 %) and > 1cm in 2,212 patients (34.4 %). The BRAFV600E mutation was significantly associated with high BMI only in patients with primary tumor size > 1cm (OR 1.034; 95% CI 1.003 – 1.065; P = 0.029), whereas no clear association was found in patients with primary tumor size ≤ 1cm (OR 1.007; 95% CI 0.984 – 1.030; P = 0.570). Gender was not a significant factor in either group.

Conclusions: Our study found that a higher BMI was positively associated with BRAFV600E mutation in patients with primary tumor size > 1cm. These results suggest that the association between BMI and BRAFV600E mutation status differs depending on primary tumor size.