余梦懿,成元华,申九妹,孙博
YU Mengyi,CHENG Yuanhua,SHEN Jiumei,SUN Bo

• 1:贵州医科大学病理学教研室
• 2:厦门市中医院病理科
• 3:贵州医科大学

摘要(Abstract)：

目的:探讨胰岛素样生长因子1受体(IGF-1R)在肝细胞癌(HCC)中的表达及意义。方法:采用免疫组织化学En Vision两步法检测HCC病例癌组织及配对癌旁组织中IGF-1R的蛋白表达,分析IGF-1R表达水平与HCC患者临床病理特征及微血管密度(MVD)的关系,同时随访观察不同IGF-1R表达水平或MVD计数HCC患者的复发、转移及死亡率。结果:HCC癌组织中IGF-1R蛋白表达水平高于癌旁组织,差异有统计学意义(P<0.05);IGF-1R高表达的HCC中,有血管浸润、病理分级Ⅲ~Ⅳ级、临床TNMⅡ~Ⅲ期患者人数多于IGF-1R低表达人数(P<0.05);癌组织中MVD值明显高于癌旁组织,差异有统计学意义(P<0.001);经Spearman等级相关分析显示IGF-1R蛋白表达水平与MVD计数呈正相关,IGF-1R高表达及MVD计数较高的HCC患者复发、转移及死亡率也较高(P<0.05)。结论:IGF-1R可促进HCC的复发、转移,与促进肿瘤血管新生有关。
Objective: To investigate the expression of insulin-like growth factor 1 receptor( IGF-1R) and the relationship between IGF-1R and the clinicopathologic features in hepatocellular carcinoma( HCC). Methods:Immunohistochemical Envision method was utilized to detect the expression of IGF-1R. MVD was marked by antibody CD34 and counted. The follow-up data of the cases of HCC was analyzed by Kaplan-Merier method for survival with log-rank test. Result:(1) The IGF-1R protein showed a higher expression in HCC than in the tumor-adjacent tissues,the difference was statistically significant( P < 0. 05).(2) The difference of the number of IGF-1R protein overexpression in histological grade and TNM stage was significant( P < 0. 05),moreover,the vascular infiltration group was significantly more than group without vascular invasion( P < 0. 05). But there was no significant difference between different tumor size,different gender,age,alcohol intake history,HBs Ag,AFP,tumor number and with or without liver cirrhosis( P > 0. 05).(3) The value of MVD was higher in HCC than that in tumor-adjacent tissues( P < 0. 05).(4) By Spearman rank correlation analysis,the level of MVD was positively correlated with IGF-1R protein expression.(5) By survival analysis of the 38 cases of HCC with follow-up data,the difference in terms of the rate of recurrence,metastasis and survival rate between the group of the high and low expression of IGF-1R protein was significant( P < 0. 05).Conclusion:IGF-1R protein may promote the occurrence and development of HCC,and promote the neovasculation in HCC. The expression of IGF-1Rcan be used as a marker to evaluate the prognosis of HCC.

关键词(KeyWords)： 癌,肝细胞;胰岛素样生长因子1受体;免疫组织化学;微血管密度;基因表达
carcinoma;hepatocellular;insulin-like growth factor 1 receptor;immunohistochemistry;vessel density;gene expression

Abstract:

Keywords:

基金项目(Foundation): 贵州省科学技术基金[黔科合J字KLG(2013)27号];贵州省科学技术基金[黔科合J字(2009)2187号];; 贵州省科技计划项目[黔科合SY字(2011)3062号];; 贵阳市科学技术计划项目[(2009)筑科农合同字第3-020号]

作者(Author): 余梦懿,成元华,申九妹,孙博
YU Mengyi,CHENG Yuanhua,SHEN Jiumei,SUN Bo

DOI: 10.19367/j.cnki.1000-2707.2016.02.007

参考文献(References)：

• [1]Forner A,Gilabert M,Bruix J,et al.Treatment of intermediate-stage hepatocellular carcinoma[J].Nat Rev Clin Oncol,2014(9):525-535.
• [2]Jemal A,Bray F,Center MM,et al.Global cancer statistics[J].CA Cancer J Clin,2011(2):69-90.
• [3]Kaseb AO,Morris JS,Hassan MM,et al.Clinical and prognostic implications of plasma insulin-like growth factor-1and vascular endothelial growth factor in patients with hepatocellular carcinoma[J].J Clin Oncol,2011(29):3892-3899.
• [4]Tsuta K,Mimae T,Nitta H,et al.Insulin-like growth factor-1 receptor protein expression and gene copy number alterations in non-small cell lung carcinomas[J].Hum Pathol,2013(6):975-982.
• [5]Hsu HH,Cheng LH,Ho TJ,et al.Apicidin-resistant HA22T hepatocellular carcinoma cells massively promote pro-survival capability viaI GF-IR/PI3K/Akt signaling pathway activation[J].Tumour Biol,2014(1):303-313.
• [6]Wang WQ,Liu L,Xu HX,et al.The combination of HTATIP2 expression and microvessel density predicts converse survival ofhepatocellular carcinoma with or without sorafenib[J].Oncotarget,2014(11):3895-3906.
• [7]Suh SJ,Yim HJ.Current status of molecular targeted therapies in hepatocellular carcinoma[J].Korean J Gastroen-terol,2013(3):136-146.
• [8]Iadevaia S,Lu Y,Morales FC,et al.Identification of optimal drug combinations targeting cellular networks:integrating phospho-proteomics and computational network analysis[J].Cancer Res,2010(17):6704-6714.
• [9]Yao WF,Liu JW,Sheng GL,et al.Blockade of IGF-IR exerts anticancer effects in hepatocellular carcinoma[J].Mol Med Rep,2011(4):719-722.
• [10]Ohshima-Hosoyama S,Hosoyama T,Nelon LD,et al.IGF-1 receptor inhibition by picropodophyllin in medulloblastoma[J].Biochem Biophys Res Commun,2010(4):727-732.
• [11]Ge YY,Shi Q,Zheng ZY,et al.MicroR NA-100 promotes the autophagy of hepatocellular carcinoma cells by inhibi-ting the expression of mT OR and?IGF-1R[J].Oncotarget,2014(15):6218-6228.
• [12]成莉,邢辉.宫颈癌IGF-IR的表达及与肿瘤血管生成、癌细胞增殖关系[J].浙江临床医学,2013(10):1461-1463.
• [13]Christopoulos PF,Msaouel P,Koutsilieris M.The role of the insulin-like growth factor-1 system in breast cancer[J].Mol Cancer,2015(1):43-43.
• [14]牛坚,赵何伟,郑苏文,等.CD90和胰岛素样生长因子1受体在原发性肝癌中的表达[J].中华普通外科杂志,2012(2):131-135.

文章评论(Comment)：