MKL1 overexpression predicts poor prognosis in patients with papillary thyroid cancer and promotes nodal metastasis
MKL1 overexpression predicts poor prognosis in patients with papillary thyroid cancer and promotes nodal metastasis
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MKL1 过表达预示甲状腺乳头状癌患者预后不良并促进淋巴结转移。
DOI：
10.1242/jcs.231399
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发表时间：
2019-08-01
影响因子：
4
通讯作者：
Zhang, Li
中科院分区：
文献类型：
--
作者：
Cheng, Xian;Xu, Shichen;Zhang, Li
甲状腺乳头状癌（PTC）是最常见的甲状腺恶性肿瘤，具有很强的颈部淋巴结转移（LNM）倾向，这增加了局部区域复发的风险，并降低了一些高危人群的生存概率。因此，迫切需要一种可靠的生物标志物来预测甲状腺癌的淋巴结转移。在本研究中，与无淋巴结转移的患者相比，有淋巴结转移的甲状腺乳头状癌患者中MKL1（也称为MRTFA）的表达显著增加。进一步的受试者工作特征（ROC）分析表明，MKL1的表达在甲状腺乳头状癌淋巴结转移的鉴别中具有诊断价值。此外，Kaplan - Meier分析显示，MKL1高表达与甲状腺乳头状癌患者的生存率显著降低有关。另外，我们的研究表明，MKL1促进甲状腺乳头状癌细胞的迁移和侵袭。在转化生长因子 - β（TGF - β）处理后，MKL1与Smad3相互作用并将其招募到MMP2启动子上以激活MMP2转录。而且，在我们的甲状腺乳头状癌患者临床标本队列中，TGF - β、MKL1和MMP2的表达之间存在显著相关性。我们的研究结果表明，检测MKL1的表达可用于预测甲状腺乳头状癌患者的颈部淋巴结转移，并为术后随访提供信息。
ABSTRACT Papillary thyroid cancer (PTC), the most common thyroid malignancy, has a strong propensity for cervical lymph node metastasis (LNM), which increases the risk of locoregional recurrence and decreases survival probability in some high-risk groups. Hence, there is a pressing requirement for a reliable biomarker to predict LNM in thyroid cancer. In the present study, MKL1 (also known as MRTFA) expression was significantly increased in PTC patients with LNM compared with those without. Further receiver operating characteristic (ROC) analysis showed that MKL1 expression had a diagnostic value in the differentiation of LNM in PTC. Furthermore, Kaplan–Meier analysis revealed that high MKL1 expression was associated with significantly decreased survival in PTC. Additionally, our study indicated that MKL1 promoted the migration and invasion of PTC cells. MKL1 interacted with and recruited Smad3 to the promoter of MMP2 to activate MMP2 transcription upon treatment with TGF-β. Moreover, there was significant correlation between expression of TGF-β, MKL1 and MMP2 in our clinical cohort of specimens from individuals with PTC. Our results suggest that the detection of MKL1 expression could be used to predict cervical LNM and inform post-operative follow-up in individuals with PTC. Summary: MKL1 expression is elevated in patients with papillary thyroid carcinoma (PTC) with nodal metastasis, promoting the migration and invasion of human PTC cells by targeting the TGF-β–Smad3–MMP2 signaling pathway.