Value of Pyruvate Carboxylase in Thyroid Fine-Needle Aspiration Wash-Out Fluid for Predicting Papillary Thyroid Cancer Lymph Node Metastasis.
Value of Pyruvate Carboxylase in Thyroid Fine-Needle Aspiration Wash-Out Fluid for Predicting Papillary Thyroid Cancer Lymph Node Metastasis.
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甲状腺细针穿刺冲洗液中丙酮酸羧化酶对甲状腺乳头状癌淋巴结转移的预测价值
DOI：
10.3389/fonc.2021.643416
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发表时间：
2021
影响因子：
4.7
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Liu C;Zhang L;Liu Y;Zhao Q;Pan Y;Zhang Y
甲状腺乳头状癌（PTC）的发病率呈上升趋势。PTC的淋巴结转移状况是决定手术和手术范围的主要因素，但目前尚无可靠的预测PTC淋巴结转移的工具，如超声不能定性诊断和有效检测中心淋巴结转移（central lymph node metastasis，CLNM）。因此，开发新的诊断生物标志物对于CLNM至关重要。代谢紊乱是与肿瘤恶性程度和转移相关的重要因素。丙酮酸羧化酶（PC）是催化丙酮酸羧化形成草酰乙酸的主要回补酶，其已被认为参与包括PTC在内的多种癌症的肿瘤发生。本研究旨在探讨PC在甲状腺细针穿刺（FNA）冲洗液中的表达对预测PTC中CLNM的作用，并探讨PC如何参与PTC的发展。首先基于公共数据库的生物信息学分析比较PTC组织和正常甲状腺组织中PC的表达水平，所述公共数据库包括基因表达谱（GEPIA）、Oncomine和基因表达综合数据库（GEO）。然后，通过RT-PCR和免疫组织化学（IHC）检测PC mRNA和蛋白表达水平，从总共42例手术证实的PTC患者的手术组织中，并比较与无CLNM患者。此外，为了评估诊断性活检中的PC表达，本研究前瞻性招募了总共71名具有超声引导下FNA冲洗液样本和细胞学诊断的甲状腺结节患者。在此基础上，我们分析了PC介导的体外PTC进展的机制。本研究表明，PC在CLNM患者的PTC组织和甲状腺FNA洗脱液样品中的表达高于无CLNM患者，PC诱导的PTC转移可能通过TGF-β/Smad调节的上皮间质转化（EMT）途径发生。
The incidence of papillary thyroid carcinoma (PTC) is increasing. Lymph node metastatic status of PTC is a major factor for decision marking of surgery and surgical extend, however, no reliable tool exists for prediction of PTC nodal metastasis, for example, ultrasound cannot qualitatively diagnose and effectively detect central lymph node metastasis (CLNM). Therefore, the development of a new diagnostic biomarker is crucial for CLNM. Metabolic dysregulation is an important factor associated with malignancy and metastasis of tumors. Pyruvate carboxylase (PC) is a major anaplerotic enzyme that catalyzes the carboxylation of pyruvate to form oxaloacetate, which has been suggested to be involved in the tumorigenesis of several cancers, including PTC. This study aimed to explore the role of PC expression in thyroid fine-needle aspiration (FNA) wash-out fluid for predicting CLNM in PTC, and to explore how PC is involved in PTC development. The expression levels of PC in PTC tissues and normal thyroid tissues were first compared based on bioinformatics analysis of public databases, including the Gene Expression Profiling (GEPIA), Oncomine and Gene Expression Omnibus (GEO) databases. Then, the PC mRNA and protein expression levels were measured by RT-PCR and Immunohistochemistry (IHC) in surgical tissues from a total of 42 patients with surgically confirmed PTC, and compared in patients with and without CLNM. Further, to assess PC expression in diagnostic biopsies, a total of 71 thyroid nodule patients with ultrasound-guided FNA wash-out fluid samples and cytological diagnosis were prospectively enrolled in the study. Then, we analyzed the mechanism of PC-mediated PTC progression in vitro. This study showed that PC expression was higher in PTC tissues and thyroid FNA wash-out fluid samples from patients with CLNM than those from patients without CLNM, and that PC-induced PTC metastasis may occur through the TGF-β/Smad-regulated epithelial–mesenchymal transition (EMT) pathway.
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影响因子：
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