CXCR4及VEGF-C在胃癌组织中的表达及其意义
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摘要
目的探讨胃癌组织中CXC趋化因子受体4(CXC chemokine receptor 4,CXCR4)和血管内皮生长因子C(vascular endothelial growth factor C,VEGF-C)的表达及其临床意义。方法采用免疫组织化学法和RT-PCR法检测290例胃癌组织和150例正常胃黏膜组织中CXCR4和VEGF-C的表达,并比较其与临床病理特征的关系。结果免疫组织化学检查显示,胃癌组织中CXCR4和VEGF-C的阳性表达率分别为83.3%和65.0%,而正常胃黏膜组织中表达均为阴性。RT-PCR检测显示,胃癌组织中CXCR4和VEGF-C mRNA表达均高于正常胃黏膜组织(均P<0.01)。胃癌组织中CXCR4 mRNA表达量在淋巴结转移方面比较,差异具有统计学意义(P<0.01),VEGF-C mRNA表达量在癌组织浸润深度和淋巴结转移方面比较,差异均具有统计学意义(均P<0.05)。CXCR4和VEGF-C mRNA在胃癌组织中的表达量呈正相关(r=0.346,P<0.05)。结论 CXCR4与VEGF-C在胃癌组织中高表达,在胃癌的发生、侵袭和转移过程中起重要作用。
Objective To study the expression of CXC chemokine receptor 4(CXCR4)and vascular endothelial growth factor C(VEGF-C) in gastric carcinoma and to investigate its clinical significance. Methods The expression of CXCR4 and VEGF-C in 290 tissue samples of gastric cancer and 150 tissue samples of normal gastric mucosa were detected by immunohistochemistry and real-time PCR,and their correlation with pathological characteristics was compared. Results The positive rates of CXCR4 and VEGF-C protein expression in gastric carcinoma were 83.3% and 65.0%, respectively, while no expression was detected in normal gastric tissue. The positive expressions of CXCR4 and VEGF-C mRNA were obviously higher in gastric cancer than those in normal gastric mucosa(P<0.01).The expression of CXCR4 mRNA was significantly different in terms of lymph node metastasis(P<0.01). The expression of VEGF-C mRNA was significantly different in terms of tumor infiltration depth and lymph node metastasis(both P<0.05). The expressions of CXCR4 and VEGF-C mRNA were positively correlated(r=0.346,P<0.05). Conclusion CXCR4 and VEGF-C were highly expressed in gastric carcinoma,that plays an important role in the tumorigenesis,progression,invasion and metastasis of gastric cancer.
Objective To study the expression of CXC chemokine receptor 4(CXCR4)and vascular endothelial growth factor C(VEGF-C) in gastric carcinoma and to investigate its clinical significance. Methods The expression of CXCR4 and VEGF-C in 290 tissue samples of gastric cancer and 150 tissue samples of normal gastric mucosa were detected by immunohistochemistry and real-time PCR,and their correlation with pathological characteristics was compared. Results The positive rates of CXCR4 and VEGF-C protein expression in gastric carcinoma were 83.3% and 65.0%, respectively, while no expression was detected in normal gastric tissue. The positive expressions of CXCR4 and VEGF-C mRNA were obviously higher in gastric cancer than those in normal gastric mucosa(P<0.01).The expression of CXCR4 mRNA was significantly different in terms of lymph node metastasis(P<0.01). The expression of VEGF-C mRNA was significantly different in terms of tumor infiltration depth and lymph node metastasis(both P<0.05). The expressions of CXCR4 and VEGF-C mRNA were positively correlated(r=0.346,P<0.05). Conclusion CXCR4 and VEGF-C were highly expressed in gastric carcinoma,that plays an important role in the tumorigenesis,progression,invasion and metastasis of gastric cancer.
引文
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[3] Yang L,Parkin DM,Ferlay J,et al.Estimates of cancer incidence in China for 2000 and projections for 2005[J].Cancer Epidemiol Biomarkers Prev,2005,14(1):243-250.
[4] Bonecchi R,Galliera E,Borroni EM,et al.Chemokines and chemokine receptors:an overview[J].Front Biosci,2009,14(3):540-551.
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[8] Kawasaki H,Altieri DC,Lu CD,et al.Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer[J].Cancer Res,1998,58(22):5071-5074.
[9] Hernandez-Bedolla MA,Carretero-Ortega J,Valadez-Sanchez M,et al.Chemotactic and proangiogenic role of calcium sensing receptor is linked to secretion of multiple cytokines and growth factors in breast cancer MDA-MB-231 cell[J].Biochim Biophys Acta,2014,1853(1):166-182.
[10] Xu H,Wu Q,Dang S,et al.Alteration of CXCR7 expression mediated by TLR4 promotes tumor cell proliferation and migration in human colorectal carcinoma[J].PLoS One,2011,6(12):e27399.
[11] Gahan JC,Gosalbez M,Yates T,et al.Chemokine and chemokine receptor expression in kidney tumors:molecular profiling of histological subtypes and association with metastasis[J].J Urol,2012,187(3):827-833.
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[13] Escot S,Blavet C,Faure E,et al.Disruption of CXCR4 signaling in pharyngeal neural crest cells causes DiGeorge syndrome-like malformations[J].Development,2016,143(4):582-588.
[14] Muller A,Homey B,Soto H,et al.Involvement of chemokine receptors in breast cancer metastasis[J].Nature,2001,410(3):50-56.
[15] Ottaiano A,Franco R,Aiello Talamanca A,et al.Over-expression of both CXC chemokine receptor 4and vascular endothelial growth factor proteins predicts early distant relapse in stage Ⅱ-Ⅲ colorectal cancer patients[J].Clin Cancer Res,2006,12(9) :2795-2803.
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[17] Retz MM,Sidhu SS,Blaveri E,et al.CXCR4 expression reflects tumor progression and regulates motility of bladder cancer cells[J].Int J Cancer,2005,114(2):182-189.
[18] Eisenhardt A,Frey U,Tack M,et al.Expression analysis and potential functional role of the CXCR4 chemokine receptor in bladder cancer[J].Eur Urol,2005,47(1):111-117.
[19] 朱元增,孙培春,吴刚,等.血管内皮生长因子C在胃癌中表达情况及对淋巴结转移作用[J].中华实用诊断与治疗杂志,2010,24(5):433-435.
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[21] Lv J,Sun H,et al.Significance of vasculogenic mimiery formation in gastric carcinoma[J].Oncol Res Treatment,2017,40(1/2):35-41.
[22] Tabernero J,Ohtsu A,Muro K,et al.Exposure-response analyses of ramucirumab from two randomized,phase Ⅲ trials of second-line treatment for advanced gastric or gastroesophageal junction cancer[J].Mol Cancer Ther,2017,16(10):2215-2222.
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