胃癌组织中VEGF-C、VEGF-D、VEGFR-3蛋白表达及其临床意义
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摘要
目的探讨胃癌原发灶、癌旁及胃周淋巴结组织中血管内皮生长因子C(VEGF-C)、血管内皮生长因子D(VEGF-D)、血管内皮生长因子受体3(VEGFR-3)蛋白表达与各临床参数的关系。方法通过免疫组化方法对60例胃癌患者的癌、癌旁及胃周淋巴结组织中VEGF-C、VEGF-D、VEGFR-3蛋白水平进行检测,并分析各临床参数包括肿瘤分化程度、Lauren分型、肿瘤浸润深度、是否有淋巴结转移、幽门螺杆菌(H.pylori)感染与否等对胃癌组织中VEGF-C、VEGF-D、VEGFR-3蛋白表达水平的影响。结果胃癌组织中VEGF-C、VEGF-D蛋白表达水平高于癌旁组织(2.82±1.66vs 2.13±1.75,4.81±2.30vs 3.78±1.94,n=60,P均<0.05)。VEGFR-3蛋白表达水平在胃癌组织和癌旁组织中差异无统计学意义(P>0.05)。胃癌转移的淋巴结组织中VEGF-C、VEGF-D、VEGFR-3的蛋白表达水平(3.77±2.43、2.86±1.95、2.55±2.11,n=44)均高于未转移淋巴结组织(2.25±2.01、1.98±1.73、0.76±1.13,n=59,P均<0.05)。关于各临床参数的分析结果显示VEGF-C、VEGF-D的蛋白表达水平在伴有淋巴结转移的胃癌组织中高于未出现淋巴结转移的胃癌组织(P<0.05),H.pylori感染阳性的胃癌组织中VEGFR-3的蛋白表达水平高于H.pylori阴性的胃癌组织(P<0.05)。结论 VEGF-C、VEGF-D蛋白表达水平在胃癌原发灶及转移淋巴结中上调,且与胃癌的淋巴转移有关。
Objective To investigate the protein expressions of vascular endothelial growth factor(VEGF)-C,VEGF-D and vascular endothelial growth factor receptor 3(VEGFR-3)in primary gastric tumor,adjacent non-tumor and perigastric lymph node tissues and their relationships with clinic-pathological features.Methods The protein levels of VEGF-C,VEGF-D and VEGFR-3 in tumor,adjacent non-tumor and perigastric lymph node tissues of 60 patients with gastric cancer were detected by immunohistochemical method.The effects of clinic-pathological features included tumor differentiation,Lauren classification,depth of tumor invasion,lymph node metastasis,and Helicobacter pylori(H.pylori)infection on VEGF-C,VEGF-D and VEGFR-3 protein levels in gastric cancer tissues were also analyzed.Results The expressions of VEGF-C and VEGF-D in gastric cancer tissues were significantly higher than those in adjacent non-tumor tissues(2.82±1.66 vs 2.13±1.75,4.81±2.30 vs 3.78±1.94;n=60;both P<0.05).There was no significant difference in VEGFR-3 protein expression between gastric cancer and adjacent non-tumor tissues(P>0.05).The expression levels of VEGF-C,VEGF-D and VEGFR-3 proteins in lymph nodes with gastric cancer metastasis(3.77±2.43,2.86±1.95,2.55±2.11;n=44)were significantly higher than those without gastric cancer metastasis(2.25±2.01,1.98±1.73,0.76±1.13;n=59;all P<0.05).Statistical analysis results showed that the expression levels of VEGF-C and VEGF-D proteins in gastric cancer tissues with lymph node metastasis were significantly higher than those without lymphatic metastasis(both P <0.05),and the VEGFR-3 expression in H.pylori-positive gastric cancer tissues was significantly higher than that in H.pylori-negative tissues(P<0.05).Conclusion VEGF-C and VEGF-D protein expressions are upregulated in primary gastric cancer tissues and related metastatic lymph node,which are correlated with lymph node metastasis of gastric cancer.
Objective To investigate the protein expressions of vascular endothelial growth factor(VEGF)-C,VEGF-D and vascular endothelial growth factor receptor 3(VEGFR-3)in primary gastric tumor,adjacent non-tumor and perigastric lymph node tissues and their relationships with clinic-pathological features.Methods The protein levels of VEGF-C,VEGF-D and VEGFR-3 in tumor,adjacent non-tumor and perigastric lymph node tissues of 60 patients with gastric cancer were detected by immunohistochemical method.The effects of clinic-pathological features included tumor differentiation,Lauren classification,depth of tumor invasion,lymph node metastasis,and Helicobacter pylori(H.pylori)infection on VEGF-C,VEGF-D and VEGFR-3 protein levels in gastric cancer tissues were also analyzed.Results The expressions of VEGF-C and VEGF-D in gastric cancer tissues were significantly higher than those in adjacent non-tumor tissues(2.82±1.66 vs 2.13±1.75,4.81±2.30 vs 3.78±1.94;n=60;both P<0.05).There was no significant difference in VEGFR-3 protein expression between gastric cancer and adjacent non-tumor tissues(P>0.05).The expression levels of VEGF-C,VEGF-D and VEGFR-3 proteins in lymph nodes with gastric cancer metastasis(3.77±2.43,2.86±1.95,2.55±2.11;n=44)were significantly higher than those without gastric cancer metastasis(2.25±2.01,1.98±1.73,0.76±1.13;n=59;all P<0.05).Statistical analysis results showed that the expression levels of VEGF-C and VEGF-D proteins in gastric cancer tissues with lymph node metastasis were significantly higher than those without lymphatic metastasis(both P <0.05),and the VEGFR-3 expression in H.pylori-positive gastric cancer tissues was significantly higher than that in H.pylori-negative tissues(P<0.05).Conclusion VEGF-C and VEGF-D protein expressions are upregulated in primary gastric cancer tissues and related metastatic lymph node,which are correlated with lymph node metastasis of gastric cancer.
引文
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[2]ZHANG J,ZHU Z,SHENG J,YU Z,YAO B,HUANG K,et al.miR-509-3-5Pinhibits the invasion and lymphatic metastasis by targeting PODXL and serves as a novel prognostic indicator for gastric cancer[J].Oncotarget,2017,8:34867-34883.
[3]COBURN N G.Lymph nodes and gastric cancer[J].J Surg Oncol,2009,99:199-206.
[4]NISHIZAWA T,SUZUKI H.Gastric carcinogenesis and underlying molecular mechanisms:helicobacter pylori and novel targeted therapy[J/OL].Biomed Res Int,2015,2015:794378.doi:10.1155/2015/794378.
[5]殷正进,李桂梅,曹晓卉.幽门螺杆菌三种检测方法的比较[J].诊断病理学杂志,2015,22:647-648.
[6]BALLA M M,DESAI S,PURWAR P,KUMAR A,BHANDARKAR P,SHEJUL Y K,et al.Differential diagnosis of lung cancer,its metastasis and chronic obstructive pulmonary disease based on serum VEGF,IL-8and MMP-9[J/OL].Sci Rep,2016,6:36065.doi:10.1038/srep36065.
[7]MORFOISSE F,RENAUD E,HANTELYS F,PRATS A C,GARMY-SUSINI B.Role of hypoxia and vascular endothelial growth factors in lymphangiogenesis[J/OL].Mol Cell Oncol,2015,2:e1024821.doi:10.1080/23723556.2015.1024821.
[8]BUI H M,ENIS D,ROBCIUC M R,MURMI H J,COHEN J,CHEN M,et al.Proteolytic activation defines distinct lymphangiogenic mechanisms for VEGFC and VEGFD[J].J Clin Invest,2016,126:2167-2180.
[9]LEI Y,LI B,TONG S,QI L,HU X,CUI Y,et al.miR-101suppresses vascular endothelial growth factor C that inhibits migration and invasion and enhances cisplatin chemosensitivity of bladder cancer cells[J/OL].PLoS One,2015,10:e0117809.doi:10.1371/journal.pone.0117809.
[10]WANG C A,JEDLICKA P,PATRICK A N,MICALIZZI D S,LEMMER K C,DEITSCH E,et al.SIX1induces lymphangiogenesis and metastasis via upregulation of VEGF-C in mouse models of breast cancer[J].J Clin Invest,2012,122:1895-1906.
[11]ACHEN M G,MANN G B,STACKER S A.Targeting lymphangiogenesis to prevent tumour metastasis[J].Br J Cancer,2006,94:1355-1360.
[12]KURENOVA E V,HUNT D L,HE D,FU A D,MASSOLL N A,GOLUBOVSKAYA V M,et al.Vascular endothelial growth factor receptor-3promotes breast cancer cell proliferation,motility and survival in vitro and tumor formation in vivo[J].Cell Cycle,2009,8:2266-2280.
[13]LI C,FAN J,SONG X,ZHANG B,CHEN Y,LI C,et al.Expression of angiopoietin-2 and vascular endothelial growth factor receptor-3 correlates with lymphangiogenesis and angiogenesis and affects survival of oral squamous cell carcinoma[J/OL].PLoS One,2013,8:e75388.doi:10.1371/journal.pone.0075388.