N-cadherin、MT1-MMP、ADAM17在甲状腺癌中的表达及其意义研究
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摘要
目的探讨N-cadherin、MT1-MMP、ADAM17在甲状腺癌中的表达及其意义。方法选取2016年1月-2017年12月期间医院行手术治疗的103例甲状腺癌患者术后甲状腺癌组织标本为观察组,另选取同期在我院行活检的65例结节性甲状腺肿病灶旁正常甲状腺组织标本为对照组,并分别监测观察组和对照组患者N-cadherin、MT1-MMP、ADAM17表达情况,并与甲状腺癌患者临床病理特征进行比较和分析。结果观察组患者N-cadherin、MT1-MMP、ADAM17的阳性表达率明显高于对照组,差异具有统计学意义(P<0.05)。Ⅲ～Ⅳ期患者N-cadherin、MT1-MMP、ADAM17的阳性表达率明显高于Ⅰ～Ⅱ期,差异具有统计学意义(P<0.05)。浸及浆膜患者N-cadherin、MT1-MMP、ADAM17的阳性表达率明显高于未及浆膜,差异具有统计学意义(P<0.05)。分化程度为低分化患者N-cadherin、MT1-MMP、ADAM17的阳性表达率明显高于中、高分化,差异具有统计学意义(P<0.05)。发生肝脏转移患者N-cadherin、MT1-MMP、ADAM17的阳性表达率明显高于未发生肝脏转移,差异具有统计学意义(P<0.05)。发生淋巴结转移患者N-cadherin、MT1-MMP、ADAM17的阳性表达率明显高于未发生淋巴结转移,差异具有统计学意义(P<0.05)。结论 N-cadherin、MT1-MMP、ADAM17在甲状腺癌的发生和发展中发挥重要作用,同时对于判断病情和预后亦具有十分重要的参考价值。
Objective To explore the expression and significance of N-cadherin,MT1-MMP and ADAM17 in thyroid cancer.Methods The specimens of thyroid cancer were selected from the observation group of 103 patients with thyroid cancer who underwent surgery from January 2016 to December 2017. During the same time,normal thyroid tissue specimens of 65 nodular goiter undergoing biopsy in the hospital were selected as the control group. The expression of N-cadherin,MT1-MMP and ADAM17 were detected in observation group and control group and compared with the clinicopathological features of thyroid cancer patients. Results The positive expression rates of N-cadherin,MT1-MMP and ADAM17 in the observation group were significantly higher than those in the control group,the differences were statistically significant(P<0.05). The positive expression rates of N-cadherin,MT1-MMP and ADAM17 in patients with stage Ⅲ～Ⅳ were significantly higher than those in patients with stage Ⅰ～Ⅱ,the differences were statistically significant(P<0.05). The positive expression rates of N-cadherin,MT1-MMP and ADAM17 in patients with serosa impregnation were significantly higher than the those in patients without serosa impregnation,the differences were statistically significant(P<0.05). The positive rate of N-cadherin,MT1-MMP and ADAM17 in patients with poorly differentiated were significantly higher than those in patients with moderately and highly differentiated,the differences were statistically significant(P<0.05). The positive expression rates of N-cadherin,MT1-MMP and ADAM17 in patients with liver metastasis were significantly higher than those in patients without liver metastasis,the differences were statistically significant(P<0.05). The positive expression rates of N-cadherin,MT1-MMP and ADAM17 in patients with lymph node metastasis were significantly higher than those in patients without lymph node metastasis,the differences were statistically significant(P<0.05). Conclusions N-cadherin,MT1-MMP and ADAM17 play an important role in the occurrence and development of thyroid cancer and have an important reference value for judging the disease condition and prognosis.
Objective To explore the expression and significance of N-cadherin,MT1-MMP and ADAM17 in thyroid cancer.Methods The specimens of thyroid cancer were selected from the observation group of 103 patients with thyroid cancer who underwent surgery from January 2016 to December 2017. During the same time,normal thyroid tissue specimens of 65 nodular goiter undergoing biopsy in the hospital were selected as the control group. The expression of N-cadherin,MT1-MMP and ADAM17 were detected in observation group and control group and compared with the clinicopathological features of thyroid cancer patients. Results The positive expression rates of N-cadherin,MT1-MMP and ADAM17 in the observation group were significantly higher than those in the control group,the differences were statistically significant(P<0.05). The positive expression rates of N-cadherin,MT1-MMP and ADAM17 in patients with stage Ⅲ～Ⅳ were significantly higher than those in patients with stage Ⅰ～Ⅱ,the differences were statistically significant(P<0.05). The positive expression rates of N-cadherin,MT1-MMP and ADAM17 in patients with serosa impregnation were significantly higher than the those in patients without serosa impregnation,the differences were statistically significant(P<0.05). The positive rate of N-cadherin,MT1-MMP and ADAM17 in patients with poorly differentiated were significantly higher than those in patients with moderately and highly differentiated,the differences were statistically significant(P<0.05). The positive expression rates of N-cadherin,MT1-MMP and ADAM17 in patients with liver metastasis were significantly higher than those in patients without liver metastasis,the differences were statistically significant(P<0.05). The positive expression rates of N-cadherin,MT1-MMP and ADAM17 in patients with lymph node metastasis were significantly higher than those in patients without lymph node metastasis,the differences were statistically significant(P<0.05). Conclusions N-cadherin,MT1-MMP and ADAM17 play an important role in the occurrence and development of thyroid cancer and have an important reference value for judging the disease condition and prognosis.
引文
[1]庞玉娟,刘文兴,高景利,等.甲状腺乳头状癌的治疗进展[J].中西医结合心血管病杂志,2016,4(32):18-19.
[2]杨进宝.甲状腺乳头状癌各亚型临床病理特点的研究进展[J].癌症进展,2015,13(1):55-60.
[3]Nadanaka S,Kinouchi H,Kitagawa H.Chondroitin sulfate-mediated N-cadherin/β-catenin signaling is associated with basal-like breast cancer cell invasion[J].J Biol Chem,2018,293(2):444-465.
[4]Cepeda MA,Pelling JJ,Evered CL,et al.The cytoplasmic domain of MT1-MMP is dispensable for migration augmentation but necessary to mediate viability of MCF-7 breast cancer cells[J].Exp Cell Res,2017,350(1):169-183.
[5]Walkiewicz K,Nowakowska-Zajdel E,Strzelczyk J,et al.Serum levels of ADAM10,ADAM12,ADAM17 AND ADAM28 in colorectal cancer patients[J].J Biol Regul Homeost Agents,2017,31(4):929-934.
[6]梁贝.甲状腺乳头状癌外科治疗进展[J].中国当代医药,2016,23(36):15-17.
[7]赵竞,刘生陈.甲状腺乳头状癌相关基因的研究进展[J].岭南现代临床外科,2016,16(6):642-646.
[8]Zhao HJ,Klausen C,Li Y,et al.Bone morphogenetic protein 2promotes human trophoblast cell invasion by upregulating N-cadherin via non-canonical SMAD2/3 signaling[J].Cell Death Dis,2018,9(2):174-178.
[9]Zhu GJ,Song PP,Zhou H,et al.Role of epithelial-mesenchymal transition markers E-cadherin,N-cadherin,β-catenin and ZEB2in laryngeal squamous cell carcinoma[J].Oncol Lett,2018,15(3):3472-3481.
[10]Waheed S,Dorjbal B,Hamilton CA,et al.Progesterone and calcitriol reduce invasive potential of endometrial cancer cells by targeting ARF6,NEDD9 and MT1-MMP[J].Oncotarget,2017,8(69):113583-113597.
[11]Yang J,Kasberg WC,Celo A,et al.Post-translational modification of the membrane type 1 matrix metalloproteinase(MT1-MMP)cytoplasmic tail impacts ovarian cancer multicellular aggregate dynamics[J].J Biol Chem,2017,292(32):13111-13121.
[12]Dosch J,Ziemke E,Wan S,et al.Targeting ADAM17 inhibits human colorectal adenocarcinoma progression and tumor-initiating cell frequency[J].Oncotarget,2017,8(39):65090-65099.
[13]Sommer A,Düppe M,Baumecker L,et al.Extracellular sphingomyelinase activity impairs TNF-α-induced endothelial cell death via ADAM17 activation and TNF receptor 1 shedding[J].Oncotarget,2017,8(42):72584-72596.
[14]Hirayama A,Awano S,Seta Y,et al.ADAM17 regulates TNF-αexpression upon lipopolysaccharide stimulation in oral keratinocytes[J].Biomed Res,2017,38(3):157-165.
[15]杨香山,程绍梅,肖瑞雪,等.Snail、N-cadherin在甲状腺乳头状癌中表达上调及其临床意义[J].中国普外基础与临床杂志,2015,22(2):181-185.
[16]陶文雅,王晨,徐韦,等.甲状腺乳头状癌组织中MMP-2、MT1-MMP的表达变化及意义[J].山东医药,2016,56(13):68-70.
[17]李晨浩,魏艳杰,田炜,等.ADAM17在甲状腺乳头状癌中表达及意义[J].基础医学与临床,2016,36(3):393-395.
[18]唐甜.RECK与MT1-MMP在甲状腺乳头状癌中的表达及意义[J].中国组织化学与细胞化学杂志,2014,23(5):423-427.
[19]呼铁民,褚会松,田甜,等.ADAM17、EGFR和Ki-67在脑胶质瘤中的表达及临床预后评估[J].中国地方病防治杂志,2017,32(6):619-620.
[20]师勇.Glactin-3、sIL-2R联合检测对于甲状腺癌的诊断价值分析[J].实验与检验医学,2018,36(6):958-960,1006.
[2]杨进宝.甲状腺乳头状癌各亚型临床病理特点的研究进展[J].癌症进展,2015,13(1):55-60.
[3]Nadanaka S,Kinouchi H,Kitagawa H.Chondroitin sulfate-mediated N-cadherin/β-catenin signaling is associated with basal-like breast cancer cell invasion[J].J Biol Chem,2018,293(2):444-465.
[4]Cepeda MA,Pelling JJ,Evered CL,et al.The cytoplasmic domain of MT1-MMP is dispensable for migration augmentation but necessary to mediate viability of MCF-7 breast cancer cells[J].Exp Cell Res,2017,350(1):169-183.
[5]Walkiewicz K,Nowakowska-Zajdel E,Strzelczyk J,et al.Serum levels of ADAM10,ADAM12,ADAM17 AND ADAM28 in colorectal cancer patients[J].J Biol Regul Homeost Agents,2017,31(4):929-934.
[6]梁贝.甲状腺乳头状癌外科治疗进展[J].中国当代医药,2016,23(36):15-17.
[7]赵竞,刘生陈.甲状腺乳头状癌相关基因的研究进展[J].岭南现代临床外科,2016,16(6):642-646.
[8]Zhao HJ,Klausen C,Li Y,et al.Bone morphogenetic protein 2promotes human trophoblast cell invasion by upregulating N-cadherin via non-canonical SMAD2/3 signaling[J].Cell Death Dis,2018,9(2):174-178.
[9]Zhu GJ,Song PP,Zhou H,et al.Role of epithelial-mesenchymal transition markers E-cadherin,N-cadherin,β-catenin and ZEB2in laryngeal squamous cell carcinoma[J].Oncol Lett,2018,15(3):3472-3481.
[10]Waheed S,Dorjbal B,Hamilton CA,et al.Progesterone and calcitriol reduce invasive potential of endometrial cancer cells by targeting ARF6,NEDD9 and MT1-MMP[J].Oncotarget,2017,8(69):113583-113597.
[11]Yang J,Kasberg WC,Celo A,et al.Post-translational modification of the membrane type 1 matrix metalloproteinase(MT1-MMP)cytoplasmic tail impacts ovarian cancer multicellular aggregate dynamics[J].J Biol Chem,2017,292(32):13111-13121.
[12]Dosch J,Ziemke E,Wan S,et al.Targeting ADAM17 inhibits human colorectal adenocarcinoma progression and tumor-initiating cell frequency[J].Oncotarget,2017,8(39):65090-65099.
[13]Sommer A,Düppe M,Baumecker L,et al.Extracellular sphingomyelinase activity impairs TNF-α-induced endothelial cell death via ADAM17 activation and TNF receptor 1 shedding[J].Oncotarget,2017,8(42):72584-72596.
[14]Hirayama A,Awano S,Seta Y,et al.ADAM17 regulates TNF-αexpression upon lipopolysaccharide stimulation in oral keratinocytes[J].Biomed Res,2017,38(3):157-165.
[15]杨香山,程绍梅,肖瑞雪,等.Snail、N-cadherin在甲状腺乳头状癌中表达上调及其临床意义[J].中国普外基础与临床杂志,2015,22(2):181-185.
[16]陶文雅,王晨,徐韦,等.甲状腺乳头状癌组织中MMP-2、MT1-MMP的表达变化及意义[J].山东医药,2016,56(13):68-70.
[17]李晨浩,魏艳杰,田炜,等.ADAM17在甲状腺乳头状癌中表达及意义[J].基础医学与临床,2016,36(3):393-395.
[18]唐甜.RECK与MT1-MMP在甲状腺乳头状癌中的表达及意义[J].中国组织化学与细胞化学杂志,2014,23(5):423-427.
[19]呼铁民,褚会松,田甜,等.ADAM17、EGFR和Ki-67在脑胶质瘤中的表达及临床预后评估[J].中国地方病防治杂志,2017,32(6):619-620.
[20]师勇.Glactin-3、sIL-2R联合检测对于甲状腺癌的诊断价值分析[J].实验与检验医学,2018,36(6):958-960,1006.
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