EDIL3在膀胱癌中的表达及与VEGF相关性的研究
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摘要
目的:观察EDIL3(EGF-like repeats and discoidin I-like domains 3)在不同分期、分级的膀胱尿路上皮癌及癌旁组织中的表达情况,探讨EDIL3在膀胱尿路上皮癌发生、发展中的作用及与血管内皮生长因子(VEGF)表达的关系。方法:采用免疫组织化学PV9001二步法检测24例膀胱癌旁组织、57例膀胱尿路上皮癌组织中EDIL3基因及VEGF基因的表达情况,结合病理分级及分期进行统计并分析两个基因表达的相关性。结果:膀胱癌组织中EDIL3基因高表达率高于癌旁组织,分别为43.9%(25/57)和16.7%(4/24)。EDIL3基因在膀胱尿路上皮癌不同分期的高表达率为非肌层浸润性尿路上皮癌(NMIBC)27.6%(8/29),肌层浸润性尿路上皮癌(MIBC)60.7%(17/28),EDIL3基因高表达率与膀胱癌分期成正相关,差异有统计学意义(P<0.05)。EDIL3基因在膀胱尿路上皮癌不同分级的高表达率为1级15.8%(3/19),2级62.5%(10/16),3级66.7%(12/18),随膀胱癌恶性程度的增加其表达率增加且该基因的表达与基因VEGF的表达呈正相关性(rs=0.239,P<0.05)。结论:EDIL3基因在膀胱尿路上皮癌中的表达与病理分级、分期和基因VEGF的表达相关,可能与膀胱癌的发生、发展及肿瘤血管形成有重要关系。
Objective:To observe the expression of EDIL3 in the tissues from adjacent cancer and bladder urothelial carcinoma with different staging and grades,and to investigate its roles in the occurrence and progress in bladder urothelial carcinoma and relationship with VEGF.Method:EDIL3and VEGF expression were evaluated in samples surrounding bladder urothelial carcinoma(n=24),specimens of bladder urothelial carcinoma(n=57)by performing immunohistochemistry with PV9001 kits and were analyzed by statistical software.Result:The expression of EDIL3 in bladder urothelial carcinoma tissues was higher than that in adjacent bladder cancer tissues(43.9% vs.16.7%,25/57 vs.4/24).EDIL3 expression was positively correlated with different staging,NMIBC 27.6%(8/29),MIBC 60.7%(17/28)respectively(P<0.05).EDIL3 expression was positively correlated with different grades,gradeⅠ 15.8%(3/19),grade Ⅱ 62.5%(10/16),grade Ⅲ 66.7%(12/18),and was positively correlated with VEGF expression(rs=0.239,P<0.05).Conclusion:The expression of EDIL3 in bladder urothelial carcinoma was associated with the grade of tumor,staging and VEGF expression.EDIL3 may play an important role in the occurrence and development of bladder cancer and tumor angiogenesis.
Objective:To observe the expression of EDIL3 in the tissues from adjacent cancer and bladder urothelial carcinoma with different staging and grades,and to investigate its roles in the occurrence and progress in bladder urothelial carcinoma and relationship with VEGF.Method:EDIL3and VEGF expression were evaluated in samples surrounding bladder urothelial carcinoma(n=24),specimens of bladder urothelial carcinoma(n=57)by performing immunohistochemistry with PV9001 kits and were analyzed by statistical software.Result:The expression of EDIL3 in bladder urothelial carcinoma tissues was higher than that in adjacent bladder cancer tissues(43.9% vs.16.7%,25/57 vs.4/24).EDIL3 expression was positively correlated with different staging,NMIBC 27.6%(8/29),MIBC 60.7%(17/28)respectively(P<0.05).EDIL3 expression was positively correlated with different grades,gradeⅠ 15.8%(3/19),grade Ⅱ 62.5%(10/16),grade Ⅲ 66.7%(12/18),and was positively correlated with VEGF expression(rs=0.239,P<0.05).Conclusion:The expression of EDIL3 in bladder urothelial carcinoma was associated with the grade of tumor,staging and VEGF expression.EDIL3 may play an important role in the occurrence and development of bladder cancer and tumor angiogenesis.
引文
1韩苏军,张思维,陈万青,等.中国膀胱癌发病现状及流行趋势分析[J].癌症进展,2013,11(1):89-95.
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3 Hidai C,Zupancic T,Penta K,et al.Cloning and characterization of developmental endothelial locus-1:An embryonic endothelial cell protein that binds theαvβ3integrinreceptor[J].Genes Dev,1998,12(1):21-33.
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6 Ciucurel E C,Sefton M V.Del-1Overexpression in Endothelial Cells Increases Vascular Density in Tissue-Engineered Implants Containing Endothelial Cells and Adipose-Derived Mesenchymal Stromal Cells[J].Tissue Eng Part A,2014,20(7-8):1235-1252.
7 Beckham C J,Olsen J,Yin P N,et al.Bladder Cancer Exosomes Contain EDIL-3/Del1and Facilitate Cancer Progression[J].J Urol,2014,192(2):583-592.
8 Hong G J,Lin N,Chen L L,et al.Association between vascular endothelial growth factor gene polymorphisms and the risk of osteonecrosis of the femoral head:Systematic review[J].Biomed Rep,2016,4(1):92-96.
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11 Sun J C,Liang X T,Pan K,et al.High expression level of EDIL3in HCC predicts poor prognosis of HCC patients[J].World J Gastroenterol,2010,16(36):4611-4615.
12 Zou X,Qiao H,Jiang X,et al.Downregulation of developmentally regulated endothelial cell locus-1inhibits the growth of colon cancer[J].J Biomed Sci,2009,16:33.
13 陈小勇,段建敏,卢建中,等.低氧诱导因子2和血管内皮生长因子在膀胱癌中的表达及意义[J].中华泌尿外科杂志,2004,25(12):52-55.
14 Urquidi V,Goodison S,Kim J,et al.Vascular endothelial growth factor,carbonic anhydrase 9,and angiogenin as urinary biomarkers for bladder cancer detection[J].Urology,2012,79(5):1185.e1-6.
15 张壮,潘剑,李一,等.舌癌中淋巴管内皮细胞具有特定的生物学表型[J].北京口腔医学,2010,18(3):121-124.
16 Damhofer H,Medema J P,Veenstra V L,et al.Assessment of the stromal contribution to Sonic Hedgehog-dependent pancreatic adenocarcinoma[J].Mol Oncol,2013,7(6):1031-1042.
17 Xia H,Chen J,Shi M,et al.EDIL3is a novel regulator of epithelial-mesenchymal transition controlling early recurrence of hepatocellular carcinoma[J].J Hepatol,2015,63(4):863-873.
18 Hajishengallis G,Chavakis T.Endogenous modulators of inflammatory cell recruitment[J].Trends Immunol,2013,34(1):1-6.
19 Schürpf T,Chen Q,Liu J H,et al.The RGD finger of Del-1is a unique structural feature critical for integrin binding[J].FASEB J,2012,26(8):3412-3420.
20 文进,李汉忠,纪志刚,等.膀胱癌受体酪氨酸激酶基因及蛋白的表达[J].中国医学科学院学报,2011,33(4):393-395.
21 Jiang S H,Wang Y,Yang J Y,et al.Overexpressed EDIL3predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer[J].Oncotarget,2016,7(4):4226-4240.
2 孔垂泽,张铭铮.膀胱癌肿瘤血管生成的研究进展[J].中华实验外科杂志,2001,18(1):92-93.
3 Hidai C,Zupancic T,Penta K,et al.Cloning and characterization of developmental endothelial locus-1:An embryonic endothelial cell protein that binds theαvβ3integrinreceptor[J].Genes Dev,1998,12(1):21-33.
4 Zhong J,Eliceiri B,Stupack D,et al.Neovascularization of ischemic tissues by gene delivery of the extracellular matrix protein Del-1[J].J Clin Invest,2003,112(1):30-41.
5 Fan Y,Zhu W,Yang M,et al.Del-1Gene Transfer Induces Cerebral Angiogenesis in Mice[J].Brain Res,2008,1219:1-7.
6 Ciucurel E C,Sefton M V.Del-1Overexpression in Endothelial Cells Increases Vascular Density in Tissue-Engineered Implants Containing Endothelial Cells and Adipose-Derived Mesenchymal Stromal Cells[J].Tissue Eng Part A,2014,20(7-8):1235-1252.
7 Beckham C J,Olsen J,Yin P N,et al.Bladder Cancer Exosomes Contain EDIL-3/Del1and Facilitate Cancer Progression[J].J Urol,2014,192(2):583-592.
8 Hong G J,Lin N,Chen L L,et al.Association between vascular endothelial growth factor gene polymorphisms and the risk of osteonecrosis of the femoral head:Systematic review[J].Biomed Rep,2016,4(1):92-96.
9 Choi E Y.Inhibition of Leukocyte Adhesion by Developmental Endothelial Locus-1(Del-1)[J].Immune Netw,2009,9(5):153-157.
10 Aoka Y,Johnson F L,Penta K,et al.The embryonic angiogenic factor Del1accelerates tumor growth by enhancing vascular formation[J].Microvasc Res,2002,64(1):148-161.
11 Sun J C,Liang X T,Pan K,et al.High expression level of EDIL3in HCC predicts poor prognosis of HCC patients[J].World J Gastroenterol,2010,16(36):4611-4615.
12 Zou X,Qiao H,Jiang X,et al.Downregulation of developmentally regulated endothelial cell locus-1inhibits the growth of colon cancer[J].J Biomed Sci,2009,16:33.
13 陈小勇,段建敏,卢建中,等.低氧诱导因子2和血管内皮生长因子在膀胱癌中的表达及意义[J].中华泌尿外科杂志,2004,25(12):52-55.
14 Urquidi V,Goodison S,Kim J,et al.Vascular endothelial growth factor,carbonic anhydrase 9,and angiogenin as urinary biomarkers for bladder cancer detection[J].Urology,2012,79(5):1185.e1-6.
15 张壮,潘剑,李一,等.舌癌中淋巴管内皮细胞具有特定的生物学表型[J].北京口腔医学,2010,18(3):121-124.
16 Damhofer H,Medema J P,Veenstra V L,et al.Assessment of the stromal contribution to Sonic Hedgehog-dependent pancreatic adenocarcinoma[J].Mol Oncol,2013,7(6):1031-1042.
17 Xia H,Chen J,Shi M,et al.EDIL3is a novel regulator of epithelial-mesenchymal transition controlling early recurrence of hepatocellular carcinoma[J].J Hepatol,2015,63(4):863-873.
18 Hajishengallis G,Chavakis T.Endogenous modulators of inflammatory cell recruitment[J].Trends Immunol,2013,34(1):1-6.
19 Schürpf T,Chen Q,Liu J H,et al.The RGD finger of Del-1is a unique structural feature critical for integrin binding[J].FASEB J,2012,26(8):3412-3420.
20 文进,李汉忠,纪志刚,等.膀胱癌受体酪氨酸激酶基因及蛋白的表达[J].中国医学科学院学报,2011,33(4):393-395.
21 Jiang S H,Wang Y,Yang J Y,et al.Overexpressed EDIL3predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer[J].Oncotarget,2016,7(4):4226-4240.