MKL1 overexpression predicts poor prognosis in patients with papillary thyroid cancer and promotes nodal metastasis

Abstract

Papillary thyroid cancer (PTC), the most common thyroid malignancy, has a strong propensity for cervical lymph node metastasis (CLNM) which will increase the risk of locoregional recurrence and decrease the survival in some high-risk groups. Hence, it is essential to set up a reliable biomarker to predict LNM in thyroid cancer. In the present study, MKL1 expression were significantly increased in PTC patients with LNM compared with those without LNM. Further ROC analysis showed that MKL1 had a diagnostic value in the differentiation of LNM in PTC (AUC=0.87, P<0.001). Meanwhile, Kaplan-Meier analysis revealed that high MKL1 expression was associated with a significant worse survival in PTC. Additionally, our study indicated that MKL1 promoted the migration and invasion of PTC cells. MKL1 interacted and recruited Smad3 to the promoter of MMP2 to activate MMP2 transcription upon TGF-β. Moreover, there were significant co-expression correlations between TGF-β, MKL1 and MMP2 in our clinical cohort of PTC specimens. Our results suggest that the detection of MKL1 expression could be used to predict CLNM and inform postoperative follow-up in papillary thyroid cancer.