Endocan在肺癌组织中的表达及其临床意义
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摘要
目的探讨endocan(endocellular-specific molecule-1,ESM-1)在原发性支气管肺癌组织中的表达,并结合临床病理资料分析其表达的临床意义。方法应用S-P免疫组织化学技术、原位杂交技术检测62例肺癌,20例非肿瘤肺组织中血管内皮细胞及癌细胞内endocan的表达。结果endocan蛋白在肺癌组织血管内皮细胞中的高表达率为70.97%(44/62),非肿瘤肺组织中血管内皮细胞的高表达率为5.00%(1/20),差异有显著性(P=0.00):在有淋巴结转移的非小细胞肺癌(Non-small celllung cancer,NSCLC)组织中血管内皮细胞endocan蛋白高表达率88.89%(32/36),明显高于无淋巴结转移组的高表达率35.29%(6/17)(P=0.00);在非小细胞肺癌组织癌细胞胞质中endocan的高表达率为62.26%(33/53),且随分化程度降低而增高,高、中分化非小细胞肺癌癌细胞胞质的高表达率为27.27%(6/22)明显低于低分化非小细胞肺癌癌细胞胞质的高表达率87.09%(27/31)(P=0.00)。而在小细胞肺癌细胞胞质中无表达。endocan mRNA在肺癌组织血管内皮细胞中的高表达率为67.74%(42/62),其中在非小细胞肺癌的高表达率为67.92%(36/53),在小细胞肺癌的高表达率为66.67%(6/9);非肿瘤肺组织中血管内皮细胞的高表达率1.50%(3/20),差异有显著性(P=0.00);而在癌细胞胞质中无表达。在有淋巴结转移的非小细胞肺癌组织血管内皮细胞中endocan mRNA高表达率80.56%(29/36),明显高于无淋巴结转移组的高表达率41.18%(7/17)(P=0.01);且随分化程度降低而增高,高、中分化非小细胞肺癌血管内皮细胞endocan mRNA高表达率63.64%(14/22)低于低分化非小细胞肺癌血管内皮细胞的高表达率70.97%(22/31)(P=0.04)。同时,发现肺癌组织中血管内皮细胞endocan蛋白和endocan mRNA表达正相关(κ=0.55,P=0.0)。且非小细胞肺癌组织中,血管内皮细胞endocan蛋白和endocan mRNA表达正相关(κ=0.55,P=0.00),癌细胞胞质endocan蛋白的表达与血管内皮细胞endocan蛋白表达正相关(κ=0.54,P=0.00),癌细胞胞质endocan蛋白的表达与血管内皮细胞endocan mRNA表达正相关(κ=0.46,P=0.00)。结论endocan及其mRNA在肺癌组织中均有高表达,肺癌组织中血管内皮细胞endocan蛋白的表达增高与淋巴结转移有关;非小细胞肺癌细胞胞质endocan蛋白的表达与肿瘤分化有关。endocan mRNA在肺癌组织血管内皮中表达与淋巴结转移和病理分级有关。血管内皮细胞endocan蛋白和endocan mRNA表达正相关。非小细胞肺癌组织中癌细胞胞质endocan蛋白和血管内皮细胞endocan蛋白、endocanmRNA表达均正相关。表明endocan参与了肺癌的发生、发展和转移。检测endocan或endocan mRNA的表达对肺癌的预后判断有一定的指导意义。抗endocan治疗可能是肺癌治疗的又一新靶点。
Purpose We evaluated the expression of endocan in lung cancer tissues and studied the clinicopathological characteristics and its clinical significance in lung cancer tissues.
Methods The 82 cases,including 62 cases of lung cancer tissues and 20 cases of nontumoral lung tissues,were evaluated by S-P immunohistochemistry / in situ hybridization(ISH).
Results The high expression rate of endocan protein in the endothelial cell of lung cancer tissues was significantly higher than that in nontumoral lung tissues (70.97%(44/62) and 5.00%(1/20),respectively),P=0.00;The high expression rate of endocan protein in the endothelia cell of NSCLC with lymph node metastasis was higher than that without lymph node metastasis(88.89%(32/36 ) and 35.29%(6/17), respectively),P=0.00;The high expression rate of endocan protein in the cytoplasm of NSCLC was 63.26%(33/53),and the high expression rate of endocan protein in the cytoplasm of NSCLC with poor differentiation was significantly higher than that with well differentiation(87.09%(27/31) and 27.27%(6/22),respectively),P=0.00.But there was no expression of endocan protein in the cytoplasm of small cell lung cancer. The high expression rate of endocan mRNA in the endothelial cell of lung cancer tissues, including 67.92%(36/53) in NSCLC and 66.67%(6/9) in SCLC,was significantly higher than that in nontumoral lung tissues(67.74%(42/62) and 10.00%(2/20), respectively),P=0.00.But there was no expression of endocan mRNA in the cytoplasm of lung cancer cell.The high expression rate of endocan mRNA in the endothelia cell of NSCLC with lymph node metastasis was higher than that without lymph node metastasis(80.56%(29/36) and 41.18%(7/17),respectively),P=0.01.The high expression rate of endocan mRNA in the endothelial cell of NSCLC with poor differentiation was significantly higher than that with well differentiation(70.97 %(22/31) and 63.64%(14/22),respectively),P=0.04.At the same time,we found that the endocan protein was positively related to endocan mRNA in endothelial cell of lung cancer tissues(κ=0.55,P=0.00).The endothelial protein was positively related to endocan mRNA in the endothelial cell of NSCLC tissues(κ=0.55,P=0.00),and the endocan protein in the cytoplasm of NSCLC was positively related to the endocan protein(κ=0.54,P=0.00) and endocan mRNA(κ=0.46,P=0.00) in the endothelial cell of lung cancer tissues.
Conclusion Both the endocan protein and endocan mRNA were highly expressed in lung cancer tissues,and the high expression of endocan protein in the endothelial cell of lung cancer tissues was related to lymph node metastasis;The endocan protein in the cytoplasm of NSCLC was related to differentiation;The expression of endocan mRNA in the lung cancer tissues was related to lymph node metastasis and pathologic grades. The endocan protein was positively related to endocan mRNA in the endothelial cell of lung cancer tissues.The endocan protein in the cytoplasm was positively related to endocan protein and endocan mRNA in the endothelial cell of NSCLC tissues.The high expression of endocan may be involved in the genesis,growth and metastasis of lung cancer.Endocan can be a new potential therapeutic target in lung cancer.
Purpose We evaluated the expression of endocan in lung cancer tissues and studied the clinicopathological characteristics and its clinical significance in lung cancer tissues.
Methods The 82 cases,including 62 cases of lung cancer tissues and 20 cases of nontumoral lung tissues,were evaluated by S-P immunohistochemistry / in situ hybridization(ISH).
Results The high expression rate of endocan protein in the endothelial cell of lung cancer tissues was significantly higher than that in nontumoral lung tissues (70.97%(44/62) and 5.00%(1/20),respectively),P=0.00;The high expression rate of endocan protein in the endothelia cell of NSCLC with lymph node metastasis was higher than that without lymph node metastasis(88.89%(32/36 ) and 35.29%(6/17), respectively),P=0.00;The high expression rate of endocan protein in the cytoplasm of NSCLC was 63.26%(33/53),and the high expression rate of endocan protein in the cytoplasm of NSCLC with poor differentiation was significantly higher than that with well differentiation(87.09%(27/31) and 27.27%(6/22),respectively),P=0.00.But there was no expression of endocan protein in the cytoplasm of small cell lung cancer. The high expression rate of endocan mRNA in the endothelial cell of lung cancer tissues, including 67.92%(36/53) in NSCLC and 66.67%(6/9) in SCLC,was significantly higher than that in nontumoral lung tissues(67.74%(42/62) and 10.00%(2/20), respectively),P=0.00.But there was no expression of endocan mRNA in the cytoplasm of lung cancer cell.The high expression rate of endocan mRNA in the endothelia cell of NSCLC with lymph node metastasis was higher than that without lymph node metastasis(80.56%(29/36) and 41.18%(7/17),respectively),P=0.01.The high expression rate of endocan mRNA in the endothelial cell of NSCLC with poor differentiation was significantly higher than that with well differentiation(70.97 %(22/31) and 63.64%(14/22),respectively),P=0.04.At the same time,we found that the endocan protein was positively related to endocan mRNA in endothelial cell of lung cancer tissues(κ=0.55,P=0.00).The endothelial protein was positively related to endocan mRNA in the endothelial cell of NSCLC tissues(κ=0.55,P=0.00),and the endocan protein in the cytoplasm of NSCLC was positively related to the endocan protein(κ=0.54,P=0.00) and endocan mRNA(κ=0.46,P=0.00) in the endothelial cell of lung cancer tissues.
Conclusion Both the endocan protein and endocan mRNA were highly expressed in lung cancer tissues,and the high expression of endocan protein in the endothelial cell of lung cancer tissues was related to lymph node metastasis;The endocan protein in the cytoplasm of NSCLC was related to differentiation;The expression of endocan mRNA in the lung cancer tissues was related to lymph node metastasis and pathologic grades. The endocan protein was positively related to endocan mRNA in the endothelial cell of lung cancer tissues.The endocan protein in the cytoplasm was positively related to endocan protein and endocan mRNA in the endothelial cell of NSCLC tissues.The high expression of endocan may be involved in the genesis,growth and metastasis of lung cancer.Endocan can be a new potential therapeutic target in lung cancer.
引文
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2 Lassalle P,Molet S,Janin A,et al.ESM-1 is a novel human endothelial cell-specific molecule expressed in lung and regulated by cytokines.J Biol.Chem,1996;271(34):20458-64
3 Timar J,Lapis K,Dudas J,et al.Proteoglycans and tumor progression:Janus-faced molecules with contradictory functions in cancer.Cancer Biol,2002;12:173-86
4 Ralph D, Sandersona, Yang Y et al. Heparan sulfate proteoglycans and heparanase—Partners in osteolytic tumor growth and metastasis.Matrix Biol, 2004 (23): 341-52
5 Bechard D, Gentina T, Delehedde M, et al.Endocan is a novel chondroitin sulfate/dermatan sulfate proteoglycan that promotes hepatocyte growth factor/scatter factor mitogenic activity.J Biol Chem, 2001; 276:48341-9
6 Scherpereel A, Gentina T, Grigoriu B, et al.Overexpression of endocan induces tumor formation.Cancer Res, 2003; 63:6084-9
7 Bechard D,Scherpereel A,Hammad H, et al.Human endothelial-cell specific molecule-1 binds directly to the integrin CD11a/CD18(LFA-1) and blocks binding to intercellular adhesion molecule-1. J Immunol, 2001; 167:3099-106
8 Hidreth JE,Gotch FM,Hildreth PD, et al.A human lymphocyte-associated antigen involved in cell-mediated lympholysis.Eur Immunol, 1983;13:202-8
9 Tachimor A, Yamada N, Sakete Y, et al.Up regulation of ICAM-1 gene expression inhibits tumour growth and liver metastasis in colorectal carcinoma.Eur J Cancer, 2005; 41:1802-10
10 Aitkenhead M,Wang SJ,Nakatsu MN,et al. Identification of endothelial cell genes expressed in an in vitro model of angiogenesis:induction of ESM-1, (β) ig-h3,and NrCAM.Microvasc Res, 2002; 63:159-71
11 Lenburg ME,Liou LS, Gerry NP,et al.Previously unidentified changes in renal cell carcinoma gene expression identified by parametric analysis of microarray data.BMC Cancer, 2003; 3:31
12 van't Veer LJ,Dai H, van de Vijver MJ,et al.Gene expression profiling predicts clinical outcome of breast cancer.Nature,2002;415:530
13 Borczuk AC,Shah L,Pearson GD,et al.Molecular signatures in biopsy specimens of lung cancer.Am J Respir Crit Care Med, 2004; 170:167-74
14 Seftor EA,Meltzcr PS,Schatteman GC, et al.Expression of multiple molecular phenotypes by aggressive melanoma tumor cells:role in vasculogenic mimicry.Crit Rev Oncol Hematol,2002;44:17-27
15 Rennel E,Mellberg S,Dimberg A,et al.Endocan is a VEGF-A and PI3K regulated gene with increased expression in human renal cancer.Exp Cell Res,2007;313(7):1285-94
16 Travis WD,Colly TV,Corrin B,et al.World Health Organization.Histological typing of lung and pleural tumours.3 rd ed,Berlin:SPringer Verlag,1999:15-41
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