生长激素受体及胰岛素样生长因子1受体在肾透明细胞癌中的表达及意义
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摘要
目的:探讨生长激素受体(growthhormonereceptor,GHR)和胰岛素样生长因子1受体(insulin-likegrowthfactor-1receptor,IGF-1R)在肾透明细胞癌组织和癌旁正常组织中的表达情况及意义。方法:采用免疫组织化学ABC法检测64例肾透明细胞癌患者的癌组织和癌旁正常组织的GHR和IGF-1R的表达情况,分析GHR和IGF-1R与肾透明细胞癌的病理分级、临床分期及肿瘤发生、发展和转移的关系。结果:GHR和IGF-1R在肾透明细胞癌的阳性表达率分别为62.50%(40/64)和75.00%(48/64),明显高于癌旁组织43.75%(28/64)和54.69%(35/64)(均P<0.05);且GHR和IGF-1 R在肾透明细胞癌组织的表达水平与肿瘤的病理分级和临床分期有关(均P <0. 0 5),与年龄及性别无相关性(均P>0.05)。GHR和IGF-1R在肾透明细胞癌组织中的表达呈线性正相关(P<0.01)。结论:GHR和IGF-1R在肾透明细胞癌组织中高表达,且两者呈线性正相关,提示GHR和IGF-1R对肾透明细胞癌的增殖起重要作用,为肾透明细胞癌的治疗提供理论依据。
Objective: To study the expression of growth hormone receptor(GHR) and insulin-like growth factor-1 receptor(IGF-1 R) in renal clear cell carcinoma and to investigate their clinical significance. Methods: The expressions of GHR and IGF-1 R protein in 64 specimens of renal clear cell carcinoma and matched paracarcinoma tissues were examined by using immunohistological ABC method and were analyzed the relationship between pathological grading, clinical stages and tumorigenesis, progression, transformation. Results: High expressions of GHR and IGF-1 R protein were observed in 62.50%(40/64) and 75.00%(48/64) of renal clear cell carcinoma tissues respectively, significantly higher than those in matched paracarcinoma tissues 43.75%(28/64) and 54.69%(35/64)(both P<0.05). The high expressions of GHR and IGF-1 R were associated with the pathological grading and clinical stages(all P<0.05), but had no relation to patient age and gender(both P>0.05). The expression of GHR was positively correlated with the expression of IGF-1 R in renal clear cell carcinoma(P<0.01). Conclusion: High expressions of GHR and IGF-1 R protein are significantly correlated in renal clear cell carcinoma, which indicate they play an important role in the proliferation renal clear cell carcinoma, and provide theoretical foundation for the treatment of renal clear cell carcinoma.
Objective: To study the expression of growth hormone receptor(GHR) and insulin-like growth factor-1 receptor(IGF-1 R) in renal clear cell carcinoma and to investigate their clinical significance. Methods: The expressions of GHR and IGF-1 R protein in 64 specimens of renal clear cell carcinoma and matched paracarcinoma tissues were examined by using immunohistological ABC method and were analyzed the relationship between pathological grading, clinical stages and tumorigenesis, progression, transformation. Results: High expressions of GHR and IGF-1 R protein were observed in 62.50%(40/64) and 75.00%(48/64) of renal clear cell carcinoma tissues respectively, significantly higher than those in matched paracarcinoma tissues 43.75%(28/64) and 54.69%(35/64)(both P<0.05). The high expressions of GHR and IGF-1 R were associated with the pathological grading and clinical stages(all P<0.05), but had no relation to patient age and gender(both P>0.05). The expression of GHR was positively correlated with the expression of IGF-1 R in renal clear cell carcinoma(P<0.01). Conclusion: High expressions of GHR and IGF-1 R protein are significantly correlated in renal clear cell carcinoma, which indicate they play an important role in the proliferation renal clear cell carcinoma, and provide theoretical foundation for the treatment of renal clear cell carcinoma.
引文
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15.郑立平,钟征翔,王晓光,等.生长激素及其受体在结直肠癌中的表达及临床意义[J].安徽医药,2016,20(2):300-303.ZHENG Liping,ZHONG Zhengxiang,WANG Xiaoguang,et al.Expression and clinical significance of growth hormone and its receptor in colorectal cancer[J].Anhui Medical and Pharmaceutical Journal,2016,20(2):300-303.
16.Franklin SL,Geffner ME.Growth hormone:the expansion of available products and indication[J].Pediatr Clin North Am,2011,58(5):1141-1165.
17.常见荣,魏练平,王荣海,等.重组人生长激素对人胃癌MGC803细胞生长的影响[J].安徽医科大学学报,2016,51(10):1411-1416.CHANG Jianrong,WEI Lianping,WANG Ronghai,et al.Effects of recombinant human growth hormone on the growth of gastric cancer MGC803 cells[J].Acta Universitis Medicinalis Anhui,2016,51(10):1411-1416.
18.周东,张毅,梁道明,等.siRNA靶向抑制GHR对人结肠癌SW480细胞增殖的影响[J].中国普通外科杂志,2011,20(9):945-950.ZHOU Dong,ZHANG Yi,LIANG Daoming,et al.Effect of siRNAtargeting inhibition of growth hormone receptor on proliferation of human colon cancer cell line SW480[J].Chinese Journal of General Surgery,2011,20(9):945-950.
19.Burtrum D,Zhu Z,Lu D,et al.A fully human monoclonal antibody to the insulin-like growth factor I receptor blocks ligand-dependent signaling and inhibits human tumor growth in vivo[J].Cancer Res,2003,63(24):8912-8921.
20.宋琦,王武玲,钱江虹.IGF-1及其受体在直肠癌中的表达和临床意义[J].中国中西医结合消化杂志,2014,22(4):195-198.SONG Qi,WANG Wuling,QIAN Jianghong.Expression and clinical significance of IGF-1 and its receptor in rectal cancer[J].Chinese Journal of Integrated Traditional and Western Medicine on Digestion,2014,22(4):195-198.
21.Gao Z,Matsue H,Wang Y,et al.Up-regulation by IGF-1 of proliferating cell nuclear antigen and Bcl-2 protein expression in human uterine leiomyoma cells[J].J Clin Endocrinol Metab,2001,86(11):5593-5913.
22.Badzio A,Wynes MW,Dziadziuszko R,et al.Increased insulin-like growth factor 1 receptor protein expression and gene copy number in small cell lung cancer[J].J Thorac Oncol,2010,5(12):1905-1911.
23.David A,Hwa V,Metherell LA,et al.Evidence for a continuum of genetic,phenotypic,and biochemical abnormalities in children with growth hormone insensitivity[J].Endocr Rev,2011,32(4):472-497.
2.马晓,胡毅,熊刚,等.生长激素受体及其基因研究进展[J].湖南农业大学学报:自然科学版,2010,36(1):58-62.MA Xiao,HU Yi,XIONG Gang,et al.Advances in research on growth hormone receptor and its gene[J].Journal of Hunan Agricultural University.Science Edition,2010,36(1):58-62.
3.Carter-Su C,Schwartz J,Argetsinger LS.Growth hormone signaling pathways[J].Growth Horm IGF Res,2016,28:11-5.
4.武广斌,黄昌明.胰岛素样生长因子I型受体肿瘤靶向治疗[J].国际肿瘤学杂志,2006,33(4):253-256.WU Guangbin,HUANG Changming.IGF-1R tumor targeted therapy[J].Journal of International Oncology,2006,33(4):253-256.
5.李江,董作亮.胰岛素样生长因子-1的研究进展[J].国际检验医学杂志,2013,34(7):848-850.LI Jiang,DONG Zuoliang.Advances in IGF-1[J].International Journal of Laboratory Medicine,2013,34(7):848-850.
6.Kashima H,Shiozawa T,Miyamoto T,et al.Autocrine stimulation of IGF1 in estrogen-induced growth of endometrial carcinoma cells:involvement of the mitogen-activated protein kinase pathway followed by up-regulation of cyclin D1 and cyclin E[J].Endocr Relat Cancer,2009,16(1):113-122.
7.唐勇民.VEGF、IGF-1及其受体在子宫内膜癌中的表达及意义[J].现代实用医学,2015,27(7):900-901.TANG Yongmin.Expression and significance of VEGF,IGF-1 and their receptors in endometrial carcinoma[J].Modern Practical Medicine,2015,27(7):900-901.
8.陈坚,刘绪顺,王康磊.生长激素受体在肝门部胆管癌中的表达及意义[J].国际肿瘤学杂志,2013,40(11):877-878.CHEN Jian,LIU Xushun,WANG Kanglei.Expression and significance of GHR in hilar cholangiocarcinoma[J].Journal of International Oncology,2013,40(11):877-878.
9.王芝艳,林汝仙,王升启.靶向胰岛素样生长因子1型受体与肿瘤治疗的研究进展[J].国外医学:药学分册,2005,32(6):361-364.WANG Zhiyan,LIN Ruxian,WANG Shengqi.Advances in targeting IGF-1R and tumor therapy[J].Foreign Medical Sciences.Section of Pharmacy,2005,32(6):361-364.
10.Moch H,Cubilla AL,Humphrey PA,et al.The 2016 WHOclassification of tumours of the urinary system and male genital organspart A:renal,penile,and testicular tumours[J].Eur Urol,2016,70(1):93-105.
11.那彦群,叶章群.中国泌尿外科疾病诊断治疗指南(2011年版)[M].北京:人民卫生出版社,2011:13-14.NA Yanqun,YE Zhangqun.Guidelines for the diagnosis and treatment of urological diseases in China(2011 edition)[M].Beijing:People’s Medical Publishing House,2011:13-14.
12.Sedek M,van der Velden LM,Strous GJ.Multimeric growth hormone receptor complexes serve as signaling platforms[J].J Biol Chem,2014,289(1):65-73.
13.Subramani R,Lopez-Valdez R,Salcido A,et al.Growth hormone receptor inhibition decreases the growth and metastasis of pancreatic ductal adenocarcinoma[J].Exp Mol Med,2014,46:e117.
14.张伟,李军,吴荣佩,等.肾透明细胞癌组织IGF-1及IGF-1R的表达及其临床意义[J].新医学,2010,41(6):371-374.ZHANG Wei,LI Jun,WU Rongpei,et al.Expression and clinical significance of IGF-1 and IGF-1R in renal clear cell carcinoma[J].New Chinese Medicine,2010,41(6):371-374.
15.郑立平,钟征翔,王晓光,等.生长激素及其受体在结直肠癌中的表达及临床意义[J].安徽医药,2016,20(2):300-303.ZHENG Liping,ZHONG Zhengxiang,WANG Xiaoguang,et al.Expression and clinical significance of growth hormone and its receptor in colorectal cancer[J].Anhui Medical and Pharmaceutical Journal,2016,20(2):300-303.
16.Franklin SL,Geffner ME.Growth hormone:the expansion of available products and indication[J].Pediatr Clin North Am,2011,58(5):1141-1165.
17.常见荣,魏练平,王荣海,等.重组人生长激素对人胃癌MGC803细胞生长的影响[J].安徽医科大学学报,2016,51(10):1411-1416.CHANG Jianrong,WEI Lianping,WANG Ronghai,et al.Effects of recombinant human growth hormone on the growth of gastric cancer MGC803 cells[J].Acta Universitis Medicinalis Anhui,2016,51(10):1411-1416.
18.周东,张毅,梁道明,等.siRNA靶向抑制GHR对人结肠癌SW480细胞增殖的影响[J].中国普通外科杂志,2011,20(9):945-950.ZHOU Dong,ZHANG Yi,LIANG Daoming,et al.Effect of siRNAtargeting inhibition of growth hormone receptor on proliferation of human colon cancer cell line SW480[J].Chinese Journal of General Surgery,2011,20(9):945-950.
19.Burtrum D,Zhu Z,Lu D,et al.A fully human monoclonal antibody to the insulin-like growth factor I receptor blocks ligand-dependent signaling and inhibits human tumor growth in vivo[J].Cancer Res,2003,63(24):8912-8921.
20.宋琦,王武玲,钱江虹.IGF-1及其受体在直肠癌中的表达和临床意义[J].中国中西医结合消化杂志,2014,22(4):195-198.SONG Qi,WANG Wuling,QIAN Jianghong.Expression and clinical significance of IGF-1 and its receptor in rectal cancer[J].Chinese Journal of Integrated Traditional and Western Medicine on Digestion,2014,22(4):195-198.
21.Gao Z,Matsue H,Wang Y,et al.Up-regulation by IGF-1 of proliferating cell nuclear antigen and Bcl-2 protein expression in human uterine leiomyoma cells[J].J Clin Endocrinol Metab,2001,86(11):5593-5913.
22.Badzio A,Wynes MW,Dziadziuszko R,et al.Increased insulin-like growth factor 1 receptor protein expression and gene copy number in small cell lung cancer[J].J Thorac Oncol,2010,5(12):1905-1911.
23.David A,Hwa V,Metherell LA,et al.Evidence for a continuum of genetic,phenotypic,and biochemical abnormalities in children with growth hormone insensitivity[J].Endocr Rev,2011,32(4):472-497.