Elevated Plasma Levels of MT4-MMP and MT6-MMP; A New Observation in Patients with Thyroid Nodules

Abstract

Background: Based on the critical role of MT4-MMP and MT6-MMP in carcinogenesis, we focused on MT4-MMP and MT6-MMP circulating levels in patients with thyroid nodules. Methods: Plasma samples were collected from three groups, including papillary thyroid cancer (PTC; n = 30), multinodular goiter (MNG; n = 30), and healthy subjects (n = 22). Enzyme-linked immunosorbent assay (ELISA) was used to obtain the concentration of MT4-MMP and MT6-MMP in the three groups. Results: Analysis of data demonstrated increased levels of MT4-MMP (PTC: 4.90 ± 1.35, MNG: 4.89 ± 1.37, and healthy: 3.13 ± 1.42) and MT6-MMP (PTC: 8.29 ± 2.50, MNG: 7.34 ± 2.09, and healthy:5.01 ± 2.13) in thyroid nodules by comparison with healthy subjects (P< 0.05). There were no significant differences in the levels of the two MT-MMPs between PTC and MNG (P> 0.05). Increased plasma levels of MT4-MMP (odds ratio = 2.48; 95% CI: 1.46–4.19; P= 0.001) or MT6-MMP (odds ratio = 1.81; 95% CI: 1.29–2.53; P= 0.001) were associated with increased risk of PTC tumorigenesis. Interestingly, a strong positive association was observed between MT4-MMP and MT6-MMP in the three groups (PTC: r = 0.766**, P= 0.000; MNG: r = 0.856**, P= 0.000; healthy r = 0.947**, P= 0.000). Areas under the ROC curve for MT4-MMP and MT6-MMP were 0.82 and 0.96, respectively. At the cutoff value > 4.7 (ng/mL), MT4-MMP and MT6-MMP showed a sensitivity of 63.3% and 90.0%, respectively, with 100% specificity. Conclusion: Our work has led us to imply that the higher levels of MT4-MMP and MT6-MMP are closely linked with both PTC and MNG tumorigenesis. They may probably promote the development of thyroid lesions; however, more research is needed to further clarify the current findings.