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.

Keywords: Glycosyl-phosphatidyl inositol; MT4-MMP; MT6-MMP; Matrix metalloproteinases; Thyroid nodules.