STAT3、Cyclin D1、ADAM12蛋白在胃黏膜癌变过程的表达及其意义
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摘要
目的:探讨STAT3、Cyclin D1、ADAM12表达在胃癌发生、发展中的作用及其临床意义。方法:采用免疫组化检测癌前疾病、癌前病变、早期胃癌、进展期胃癌组织及转移淋巴结组织中STAT3、Cyclin D1、ADAM12的表达,分析这3个基因表达在胃组织癌变过程中的作用。结果:STAT3阳性表达率及Cyclin D1阳性表达率在早期及进展期胃癌、转移淋巴结中表达增高,差异有统计学意义(P<0.01);Cyclin D1、STAT3蛋白表达与胃癌的分化程度及淋巴结转移呈正相关(P<0.05);ADAM12蛋白表达阳性率在各组间均无统计学差异(P>0.05);STAT3与Cyclin D1表达呈正相关(r=0.305,P<0.01)。结论:STAT3、Cyclin D1与胃癌的发展及侵袭转移相关,STAT3可能通过上调Cyclin D1的表达促进胃癌的发展及转移。
Objective: To investigate the role of STAT3, Cyclin D1 and ADAM12 expression in the occurrence and development of gastric cancer and its clinical significance. Methods: The expression of STAT3, Cyclin D1 and ADAM12 in precancerous diseases, precancerous lesions, early gastric cancer, advanced gastric cancer and metastatic lymph nodes was detected by immunohistochemistry, and their roles in the carcinogenesis of gastric tissue were analyzed. Results: The positive expression rates of STAT3 and Cyclin D1 were significantly higher in early and advanced gastric cancer and metastatic lymph nodes(P<0.01). The expression of Cyclin D1 and STAT3 protein was positively correlated with the differentiation degree and lymph node metastasis of gastric cancer(P<0.05). The positive rate of ADAM12 protein expression was not significantly different among the groups(P>0.05). STAT3 is positively correlated with Cyclin D1 expression(r=0.305,P<0.01). Conclusion: STAT3 and Cyclin D1 are related to the development, invasion and metastasis of gastric cancer. STAT3 may promote the development and metastasis of gastric cancer by up-regulating the expression of Cyclin D1.
Objective: To investigate the role of STAT3, Cyclin D1 and ADAM12 expression in the occurrence and development of gastric cancer and its clinical significance. Methods: The expression of STAT3, Cyclin D1 and ADAM12 in precancerous diseases, precancerous lesions, early gastric cancer, advanced gastric cancer and metastatic lymph nodes was detected by immunohistochemistry, and their roles in the carcinogenesis of gastric tissue were analyzed. Results: The positive expression rates of STAT3 and Cyclin D1 were significantly higher in early and advanced gastric cancer and metastatic lymph nodes(P<0.01). The expression of Cyclin D1 and STAT3 protein was positively correlated with the differentiation degree and lymph node metastasis of gastric cancer(P<0.05). The positive rate of ADAM12 protein expression was not significantly different among the groups(P>0.05). STAT3 is positively correlated with Cyclin D1 expression(r=0.305,P<0.01). Conclusion: STAT3 and Cyclin D1 are related to the development, invasion and metastasis of gastric cancer. STAT3 may promote the development and metastasis of gastric cancer by up-regulating the expression of Cyclin D1.
引文
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[2]左婷婷,郑荣寿,曾红梅,等.中国胃癌流行病学现状[J].中国肿瘤临床,2017,44(1):52-58.
[3] MONIREH H,ZUHAIR M H,MARZIEH E,et al.STAT3 is overactivated in gastric cancer[J].Stem-Like Cells,2016,17(4):617-628.
[4] 周洪涛,李山林,刘学进.Cyclin D1及TNFR1在腺瘤性息肉与胃癌中的表达意义[J].实用癌症杂志,2019,34(2):187-190.
[5] CIREAP N,NARITA D.Molecularprofiling of ADAM12 and ADAM17 genes in human malignant melanoma[J].Pathol & Oncol Res,2013,19:755-762.
[6] JIANG D,LI H,XIANG H,et al.Long chain non-coding RNA(lncRNA)HOTAIR knockdown increases miR-454-3p to suppress gastric cancer growth by targeting STAT3/cyclin D1[J].Med Sci Monit,2019,27(25):1537-1548.
[7] DEEPAK R V,SINTO M S,THOMAS S,et al.Cyclin D1 overexpression associated with activation of STAT3 in oral carcinoma patients from South India[J].Cancer Res Ther,2018,14(2):403-408.
[8] ROY R,DAGHER A,BUTTERFIELD C.ADAM12 is a novel regulator of tumor angiogenesis via STAT3 signaling[J].Mol Cancer Res,2017,15(11):1608-1622.
[9] 范尧夫,魏睦新.胃癌癌前病变的研究进展及防治对策[J].世界华人消化杂志,2012,20(20):1807-1812.
[10] 岳原亦,吴思,王爽,等.STATs家族在结直肠癌中的研究进展[J].现代肿瘤医学,2018,26(17):2776-2780.
[11] 杨毅,袁杰,牛瑞芳.STAT3的多重调控方式在肿瘤中的研究进展[J].中国肿瘤临床,2016,43(8):352-357.
[12] YU L F,CHENG Y,QIAN M M,et al.Activation of STAT3 signaling in human stomach adenocarcinoma drugresistant cell line and its relationship with expression of vascular endothelial growth factor[J].World J Gastroenterol,2005,11(6):875-879.
[13] YU R X,YU R T,LIU Z.Inhibition of two gastric cancer cell lines induced by fucoxanthin involves downregulation of Mcl-1 and STAT3[J].Hum Cell,2018,31(1):50-63.
[14] YU S,LI G,WANG Z,et al.The prognostic value of pSTAT3 in gastric cancer:a meta-analysis[J].Cancer Res Clin Oncol,2016,142(3):649-657.
[15] YAKATA Y,NAKAYAMA T,YOSHIZAKI A,et al.Expression of p-STAT3 in human gastric carcinoma:significant correlation in tumour invasion and prognosis[J].Int J Oncol,2007,30(2):437-442.
[16] ZHAO J,DONG Y,KANG W,et al.Helicobacter pylori-induced STAT3 activation and signalling network in gastric cancer[J].Oncoscience,2014,1(6):468-475.
[17] JOHN R R,MALATHI N,RAVINDRAN C,et al.Multifaceted role played by cyclin D1 in tumor behavior[J].Indian J Dent Res,2017,28(2):187-192.
[18] CARL-MCGRATH S,LENDECKEL U,EBERT M,et al.The disintegrin-metalloproteinases ADAM9,ADAM12,and ADAM15 are upregulated in gastric cancer[J].Int J Oncol,2005,26(1):17-24.
[19] FANG W,QIAN J,WU Q,et al.ADAM-17 expression is enhanced by FoxM1and is a poor prognostic sign in gastric carcinoma[J].J Surg Res,2017,220:223-233.