超声引导下甲状腺结节细针穿刺活检组织中BRD4、Skp2表达量与结节病理特征的相关性
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摘要
目的:研究超声引导下甲状腺结节细针穿刺活检组织中溴样结构域蛋白4(BRD4)和S期激酶相关蛋白2(Skp2)表达量与结节病理特征的相关性。方法:选择2015年3月～2018年3月本院超声引导下甲状腺结节细针穿刺活检获取的组织,根据病理结果分为恶性组和良性组,检测BRD4、Skp2及增殖基因、血管新生基因的表达量。结果:恶性组甲状腺结节中BRD4、Skp2的mRNA表达量明显高于良性组且恶性组中TNMⅢ～Ⅳ期、有包膜侵犯、存在淋巴结转移的甲状腺结节中BRD4、Skp2的mRNA表达量明显高于TNM I～Ⅱ期、无包膜侵犯、无淋巴结转移的甲状腺结节;恶性组甲状腺结节中细胞周期蛋白D1(CCND1)、β-连环蛋白(β-catenin)、细胞核增殖抗原(PCNA)、血管内皮生长因子(VEGF)、内皮细胞特异分子-1(ESM-1)、生存素(Survivin)、环氧合酶2(COX2)的mRNA表达量明显高于良性组且与BRD4、Skp2呈正相关,细胞周期蛋白G2(CCNG2)、内皮抑素(ES)的mRNA表达量明显低于良性组且与BRD4、Skp2呈负相关。结论:甲状腺恶性结节中BRD4、Skp2的高表达与病理特征的改变相关且能够改变增殖基因、血管新生基因的表达。
Objective: To study the correlation of bromodomain-containing protein 4(BRD4) and S-phase kinase-associated protein 2(Skp2) expression levels in ultrasound-guided thyroid nodule fine needle aspiration biopsy tissue with the pathological features of nodules. Methods: The tissues obtained in ultrasound-guided thyroid nodule fine needle aspiration biopsy in our hospital between March 2015 and March 2018 was selected and divided into malignant group and benign group according to the pathological results, and the expression levels of BRD4, Skp2, proliferation genes and angiogenesis genes were detected. Results: The BRD4 and Skp2 mRNA expression in thyroid nodules of the malignant group were significantly higher than those of the benign group, and the BRD4 and Skp2 mRNA expression in the malignant group of thyroid nodules with TNM Ⅲ～Ⅳ, capsular invasion and lymph node metastasis were significantly higher than those in the thyroid nodules with TNM I～Ⅱ, without capsular invasion and without lymph node metastasis; cyclin D1(CCND1), β-catenin, proliferation cell nuclear antigen(PCNA), vascular endothelial growth factor(VEGF), endothelial cell specific molecule-1(ESM-1), Survivin and cyclooxygenase 2(COX2) mRNA expression in thyroid nodules of the malignant group were obviously higher than those of the benign group and positively correlated with BRD4 and Skp2 while cyclin G2(CCNG2) and endostatin(ES) mRNA expression were significantly lower than those of the benign group and negatively correlated with BRD4 and Skp2. Conclusion:The high expression of BRD4 and Skp2 in malignant thyroid nodules is correlated with the pathological changes and can change the expression of proliferation genes and angiogenesis genes.
Objective: To study the correlation of bromodomain-containing protein 4(BRD4) and S-phase kinase-associated protein 2(Skp2) expression levels in ultrasound-guided thyroid nodule fine needle aspiration biopsy tissue with the pathological features of nodules. Methods: The tissues obtained in ultrasound-guided thyroid nodule fine needle aspiration biopsy in our hospital between March 2015 and March 2018 was selected and divided into malignant group and benign group according to the pathological results, and the expression levels of BRD4, Skp2, proliferation genes and angiogenesis genes were detected. Results: The BRD4 and Skp2 mRNA expression in thyroid nodules of the malignant group were significantly higher than those of the benign group, and the BRD4 and Skp2 mRNA expression in the malignant group of thyroid nodules with TNM Ⅲ～Ⅳ, capsular invasion and lymph node metastasis were significantly higher than those in the thyroid nodules with TNM I～Ⅱ, without capsular invasion and without lymph node metastasis; cyclin D1(CCND1), β-catenin, proliferation cell nuclear antigen(PCNA), vascular endothelial growth factor(VEGF), endothelial cell specific molecule-1(ESM-1), Survivin and cyclooxygenase 2(COX2) mRNA expression in thyroid nodules of the malignant group were obviously higher than those of the benign group and positively correlated with BRD4 and Skp2 while cyclin G2(CCNG2) and endostatin(ES) mRNA expression were significantly lower than those of the benign group and negatively correlated with BRD4 and Skp2. Conclusion:The high expression of BRD4 and Skp2 in malignant thyroid nodules is correlated with the pathological changes and can change the expression of proliferation genes and angiogenesis genes.
引文
1 Nordio M,Basciani S.Evaluation of thyroid nodule characteristics in subclinical hypothyroid patients under a myo-inositol plus selenium treatment[J].Eur Rev Med Pharmacol Sci,2018,22(7):2153-2159.
2 Girardi FM.Thyroid carcinoma pattern presentation according to age [J].Int Arch Otorhinolaryngol,2017,21(1):38-41.
3 Xu XL,Li Z,Liu A,et al.SKP2 Activation by thyroid hormone receptor β2 bypasses rb-dependent proliferation in rb-deficient cells[J].Cancer Res,2017,77(24):6838-6850.
4 冀凯伦,刘琪,牟作峰,等.BRD4通过SHH信号通路诱导甲状腺癌细胞增殖、侵袭与迁移[J].中国癌症杂志,2017,27(11):860-866.
5 高献争,李文才,刁长英,等.BRD4在鳞状细胞癌中的表达及其对鳞状细胞癌细胞增殖和侵袭的影响[J].中华病理学杂志,2018,47(5):344-348.
6 王铮,朱金玉,胡述提.溴结构域结合蛋白4在人食管鳞状细胞癌组织的表达及意义[J].中华实验外科杂志,2017,34(12):2249-2251.
7 刘求梅,刘洁,刘映.Skp2与p27kip1在人子宫颈鳞癌中的表达及其与HPV感染的关系[J].实用肿瘤杂志,2016,31(5):429-433.
8 Pratheeshkumar P,Siraj AK,Divya SP,et al.Downregulation of SKP2 in papillary thyroid cancer acts synergistically with trail on inducing apoptosis via ros[J].J Clin Endocrinol Metab,2018,103(4):1530-1544.
9 王倩倩,李伟娟,刘阁玲,等.细胞周期蛋白G2在人甲状腺乳头状癌K1细胞中的表达及其对K1细胞增殖凋亡的影响[J].肿瘤防治研究,2017,44(7):460-464.
10 何晓燕,李成烈.甲状腺乳头状癌中PTEN和CyclinD1的表达及临床意义[J].中华内分泌外科杂志,2018,12(2):136-139.
11 Temiz P,Akka? G,Ne?e N,et al.Determination-of apoptosis and cell cycle modulators (p16,p21,p27,p53,BCL-2,Bax,BCL-xL,and cyclin D1) in thyroid follicular carcinoma,follicular adenoma,and adenomatous nodules via a tissue microarray method[J].Turk J Med Sci,2015,45(4):865-871.
12 徐晓武,张银龙,朱少俊,等.TRβ1、β-catenin及Cyclin A2在甲状腺乳头状癌的表达及临床意义[J].医学研究杂志,2017,46(5):99-103.
13 彭焱,吴翠娇,向桂玲.甲状腺癌组织中神经细胞黏附分子、β-catenin 的表达及意义[J].山东医药,2017,57(6):98-100.
14 魏丽.CK19、CD56与 PCNA 在甲状腺乳头状癌与乳头状增生中的表达及意义[J].中华普外科手术学杂志(电子版),2016,10(5):599-601.
15 Marotta V,Sciammarella C,Capasso M,et al.Preliminary data of VEGF-A and VEGFR-2 polymorphisms as predictive factors of radiological response and clinical outcome in iodine-refractory differentiated thyroid cancer treated with sorafenib[J].Endocrine,2017,57(3):539-543.
16 李锐,李晓丽.甲状腺癌患者癌组织中CD34、增殖细胞核抗原和内皮细胞特异分子-1的表达及意义[J].中国老年医学,2018,38(16):3881-3883.
17 段睿,刘正人,张浩.Survivin siRNA对甲状腺乳头状癌细胞裸鼠移植瘤血管生成的影响[J].海南医学,2015,26(1):5-6,7.
18 Selemetjev S,Savin S,Paunovic I,et al.Concomitant high expression of survivin and vascular endothelial growth factor-C is strongly associated with metastatic status of lymph nodes in papillary thyroid carcinoma[J].J Cancer Res Ther,2018,14(Supplement):114-119.
19 贾宗良,朱宏升,柴明明,等.甲状腺乳头状癌中 MMP2、COX-2、VEGF 和MVD 的表达及临床意义[J].西安交通大学学报(医学版),2015,3:362-367,382.
20 左湘川,胡淑芳,荣太梓.分化型甲状腺癌术后复发或转移患者血清内皮抑素和血管内皮生长因子水平变化及临床意义[J].中国综合临床,2017,33(12):1101-1104.
2 Girardi FM.Thyroid carcinoma pattern presentation according to age [J].Int Arch Otorhinolaryngol,2017,21(1):38-41.
3 Xu XL,Li Z,Liu A,et al.SKP2 Activation by thyroid hormone receptor β2 bypasses rb-dependent proliferation in rb-deficient cells[J].Cancer Res,2017,77(24):6838-6850.
4 冀凯伦,刘琪,牟作峰,等.BRD4通过SHH信号通路诱导甲状腺癌细胞增殖、侵袭与迁移[J].中国癌症杂志,2017,27(11):860-866.
5 高献争,李文才,刁长英,等.BRD4在鳞状细胞癌中的表达及其对鳞状细胞癌细胞增殖和侵袭的影响[J].中华病理学杂志,2018,47(5):344-348.
6 王铮,朱金玉,胡述提.溴结构域结合蛋白4在人食管鳞状细胞癌组织的表达及意义[J].中华实验外科杂志,2017,34(12):2249-2251.
7 刘求梅,刘洁,刘映.Skp2与p27kip1在人子宫颈鳞癌中的表达及其与HPV感染的关系[J].实用肿瘤杂志,2016,31(5):429-433.
8 Pratheeshkumar P,Siraj AK,Divya SP,et al.Downregulation of SKP2 in papillary thyroid cancer acts synergistically with trail on inducing apoptosis via ros[J].J Clin Endocrinol Metab,2018,103(4):1530-1544.
9 王倩倩,李伟娟,刘阁玲,等.细胞周期蛋白G2在人甲状腺乳头状癌K1细胞中的表达及其对K1细胞增殖凋亡的影响[J].肿瘤防治研究,2017,44(7):460-464.
10 何晓燕,李成烈.甲状腺乳头状癌中PTEN和CyclinD1的表达及临床意义[J].中华内分泌外科杂志,2018,12(2):136-139.
11 Temiz P,Akka? G,Ne?e N,et al.Determination-of apoptosis and cell cycle modulators (p16,p21,p27,p53,BCL-2,Bax,BCL-xL,and cyclin D1) in thyroid follicular carcinoma,follicular adenoma,and adenomatous nodules via a tissue microarray method[J].Turk J Med Sci,2015,45(4):865-871.
12 徐晓武,张银龙,朱少俊,等.TRβ1、β-catenin及Cyclin A2在甲状腺乳头状癌的表达及临床意义[J].医学研究杂志,2017,46(5):99-103.
13 彭焱,吴翠娇,向桂玲.甲状腺癌组织中神经细胞黏附分子、β-catenin 的表达及意义[J].山东医药,2017,57(6):98-100.
14 魏丽.CK19、CD56与 PCNA 在甲状腺乳头状癌与乳头状增生中的表达及意义[J].中华普外科手术学杂志(电子版),2016,10(5):599-601.
15 Marotta V,Sciammarella C,Capasso M,et al.Preliminary data of VEGF-A and VEGFR-2 polymorphisms as predictive factors of radiological response and clinical outcome in iodine-refractory differentiated thyroid cancer treated with sorafenib[J].Endocrine,2017,57(3):539-543.
16 李锐,李晓丽.甲状腺癌患者癌组织中CD34、增殖细胞核抗原和内皮细胞特异分子-1的表达及意义[J].中国老年医学,2018,38(16):3881-3883.
17 段睿,刘正人,张浩.Survivin siRNA对甲状腺乳头状癌细胞裸鼠移植瘤血管生成的影响[J].海南医学,2015,26(1):5-6,7.
18 Selemetjev S,Savin S,Paunovic I,et al.Concomitant high expression of survivin and vascular endothelial growth factor-C is strongly associated with metastatic status of lymph nodes in papillary thyroid carcinoma[J].J Cancer Res Ther,2018,14(Supplement):114-119.
19 贾宗良,朱宏升,柴明明,等.甲状腺乳头状癌中 MMP2、COX-2、VEGF 和MVD 的表达及临床意义[J].西安交通大学学报(医学版),2015,3:362-367,382.
20 左湘川,胡淑芳,荣太梓.分化型甲状腺癌术后复发或转移患者血清内皮抑素和血管内皮生长因子水平变化及临床意义[J].中国综合临床,2017,33(12):1101-1104.