Overexpression of G Protein-Coupled Receptor Kinase 6 (GRK6) Is Associated with Progression and Poor Prognosis of Papillary Thyroid Carcinoma.
Overexpression of G Protein-Coupled Receptor Kinase 6 (GRK6) Is Associated with Progression and Poor Prognosis of Papillary Thyroid Carcinoma.
复制标题
G蛋白偶联受体激酶6（GRK6）的过表达与乳头状甲状腺癌的进展和预后不良有关。
DOI：
10.12659/msm.908176
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发表时间：
2018-05-28
期刊：
影响因子：
--
通讯作者：
Xue J
中科院分区：
文献类型：
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作者：
Che X;Zhang G;Zhang X;Xue J
大约20%的甲状腺乳头状癌（PTC）患者会出现癌症复发，但尚未确定临床可用的生物标志物。本研究旨在评价G蛋白偶联受体激酶6（GRK 6）在PTC中的预后价值。我们回顾性纳入了108例PTC患者，并通过RT-qPCR和免疫组织化学（IHC）检测了GRK 6在切除肿瘤样本中的表达。临床资料以卡方检定、单因素分析及多因素分析。为了研究GRK 6在调节PTC进展中的功能机制，我们还在TPC-1细胞中进行了过表达和沉默实验，TPC-1细胞是由PTC组织产生的细胞系。RT-qPCR结果显示PTC中GRK 6-mRNA的水平高于邻近甲状腺组织。免疫组化结果显示GRK 6在PTC中的蛋白表达模式不同。因此，我们将患者分为低GRK 6组和高GRK 6组。卡方检验显示，GRK 6越高，肿瘤越大（P=0.045），TNM分期越晚（P=0.001）。Kaplan-Meier生存曲线和logrank检验显示，PTC患者GRK 6水平越高，无病生存期（DFS）越差（P=0.002）。此外，考克斯回归分析证实GRK 6是PTCs复发风险较高的独立预后因素（P=0.047）。MTT法和Transwell法检测表明GRK 6过表达可显著增强肿瘤的增殖和侵袭能力，与临床结果一致。我们的数据显示GRK 6在促进PTC进展中的致癌作用。
Approximately 20% of patients with papillary thyroid carcinoma (PTC) will develop cancer recurrence, but no clinically available biomarker has been identified. Our study aimed to evaluate the prognostic value of G protein-coupled receptor kinase 6 (GRK6) in PTCs. We retrospectively enrolled 108 PTC patients in this study, and explored the expression of GRK6 in resected tumor samples by RT-qPCR and immunohistochemistry (IHC). The clinical data were interpreted by chi-square test, univariate analysis, and multivariate analysis. To investigate the functional mechanisms of GRK6 in regulating PTC progression, we also performed overexpression and silencing experiments in TPC-1 cells, a cell line generated from PTC tissues. RT-qPCR results showed a higher level of GRK6-mRNA in PTCs than in adjacent thyroid tissues. IHC revealed a distinct protein expression pattern of GRK6 among PTCs. Accordingly, we classified patients into low-GRK6 and high-GRK6 groups. The chi-square test showed that a higher GRK6 was associated with larger tumor size (P=0.045) and advanced TNM stage (P=0.001). Kaplan-Meier survival curve and log rank test demonstrated that higher GRK6 predicted poor disease-free survival (DFS) in PTC patients (P=0.002). Furthermore, Cox regression analysis confirmed that GRK6 was an independent prognostic factor for a higher recurrence risk of PTCs (P=0.047). MTT assay and Transwell assay demonstrated that GRK6 overexpression can significantly enhance tumor proliferation and invasion, which was consistent with clinical findings. Our data show the oncogenic effects of GRK6 in promoting PTC progression.