食管鳞癌中CD151、ERK1/2及血管生成拟态的表达及临床意义
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摘要
[目的]研究组织分化抗原151(CD151)及细胞外调节蛋白激酶1/2(ERK1/2)在食管鳞状细胞癌(ESCC)中的表达情况,分析两者表达与血管生成拟态(VM)的相关性。[方法]选取100例存档石蜡包埋ESCC组织标本作为观察组和50例癌旁(≥5cm)正常食管组织作为对照组,采用免疫组织化学ElivisionTMplus法检测ESCC中CD151及ERK1/2的表达,运用CD34/PAS双染检测食管癌中VM存在情况;并用Kaplan-Meier法分析VM与预后的关系。[结果 ]观察组CD151(82%)、ERK1/2(75%)蛋白阳性表达率及VM存在率(29%)均明显高于对照组(10%、36%、8%)(P均<0.05)。CD151蛋白表达与ESCC的浸润深度、淋巴结转移、临床分期、分化程度有关(P均<0.05);ERK1/2蛋白表达与ESCC的淋巴结转移、临床分期、分化程度有关(P均<0.05);ERK1/2在CD151阳性组的表达明显高于CD151阴性组,且两者表达呈正相关(r=0.451,P<0.001);CD151和ERK1/2表达均与VM存在呈正相关(r=0.299,P=0.002;r=0.318,P=0.001)。Kaplan-Meier生存分析显示有VM组与无VM组5年生存率分别为10.3%和50.7%(P<0.05)。Cox多因素回归分析显示:浸润深度、临床分期、VM存在是食管鳞癌患者术后5年生存率的独立影响因素(P均<0.05)。[结论] CD151、ERK1/2在食管鳞癌的发生及发展中具有重要作用,可能通过VM的形成,影响食管鳞癌的发生发展、转移及预后。
[Objective] To investigate the expression of tissue differentiation antigen 151(CD151)and extracellular regulated protein kinase1/2(ERK1/2) in esophageal squamous cell carcinoma(ESCC),and to analyze the their correlation with vasculogenic mimicry(VM). [Methods] One hundred samples of paraffin-embedded ESCC tissue and 50 samples of normal esophageal tissues were collected. The expression of CD151 and ERK1/2 in ESCC was detected by ElivisionTM plus method. The VM in esophageal cancer was detected by CD34/PAS double staining. The relationship between VM and prognosis was analyzed by Kaplan-Meier method. [Results] The positive rate of CD151(82%),ERK1/2(75%) and the present rate of VM(29%) in the ESCC group were significantly higher than those in the control group(10%,36%,8%;all P<0.05). The expression of CD151 protein was correlated with the depth of invasion,lymph node metastasis,clinical stage and degree of differentiation of ESCC(all P<0.05). The expression of ERK1/2 protein was correlated with lymph node metastasis,clinical stage and differentiation of ESCC(all P<0.05). The expression of ERK1/2 was positively correlated with the expression of CD151 in ESCC(r=0.451,P<0.001);the expression of CD151 and ERK1/2 was positively correlated with VM(r=0.299,P=0.002;r=0.318,P=0.001). Kaplan-Meier survival curve showed that the 5-years survival rate of VM group and non-VM group was 10.3% and 50.7%,respectively(P<0.05). Cox multivariate regression analysis demonstrated that the depth of invasion,clinical stage and VM were the independent factors of the 5-years survival(P<0.05). [Conclusion] The expression of CD151 and ERK1/2 are upregulated in ESCC,which may affect the development,metastasis and prognosis of ESCC through VM formation.
[Objective] To investigate the expression of tissue differentiation antigen 151(CD151)and extracellular regulated protein kinase1/2(ERK1/2) in esophageal squamous cell carcinoma(ESCC),and to analyze the their correlation with vasculogenic mimicry(VM). [Methods] One hundred samples of paraffin-embedded ESCC tissue and 50 samples of normal esophageal tissues were collected. The expression of CD151 and ERK1/2 in ESCC was detected by ElivisionTM plus method. The VM in esophageal cancer was detected by CD34/PAS double staining. The relationship between VM and prognosis was analyzed by Kaplan-Meier method. [Results] The positive rate of CD151(82%),ERK1/2(75%) and the present rate of VM(29%) in the ESCC group were significantly higher than those in the control group(10%,36%,8%;all P<0.05). The expression of CD151 protein was correlated with the depth of invasion,lymph node metastasis,clinical stage and degree of differentiation of ESCC(all P<0.05). The expression of ERK1/2 protein was correlated with lymph node metastasis,clinical stage and differentiation of ESCC(all P<0.05). The expression of ERK1/2 was positively correlated with the expression of CD151 in ESCC(r=0.451,P<0.001);the expression of CD151 and ERK1/2 was positively correlated with VM(r=0.299,P=0.002;r=0.318,P=0.001). Kaplan-Meier survival curve showed that the 5-years survival rate of VM group and non-VM group was 10.3% and 50.7%,respectively(P<0.05). Cox multivariate regression analysis demonstrated that the depth of invasion,clinical stage and VM were the independent factors of the 5-years survival(P<0.05). [Conclusion] The expression of CD151 and ERK1/2 are upregulated in ESCC,which may affect the development,metastasis and prognosis of ESCC through VM formation.
引文
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[11]Zhang X,Song Q,Wei C,et al.LRIG1 inhibits hypoxiainduced vasculogenic mimicry formation via suppression of the EGFR/PI3K/AKT pathway and epithelial-to-mesenchymal transitionin human glioma SHG-44 cells[J].Cell Stress Chaperones,2015,20(4):631-641.
[12]Lu XS,Sun W,Ge CY,et al.Contribution of the PI3K/MMPs/Ln-5γ2 andEphA2/FAK/Paxillin signaling pathways to tumor growth and vasculogenic mimicry of gallbladder carcinomas[J].Int J Oncol,2013,42(6):2103-2115.
[13]Zuo H,Liu Z,Liu X,et al.CD151 gene delivery after myocardial infarction promotes functional neovascularization and activates FAK signaling[J].Mol Med,2009,15(9-10):307-315.
[14]Zhang J,Gao Q,Zhou Y,et al.Focal adhesion kinase-promoted tumor glucose metabolism is associated with a shift of mitochondrial respiration to glycolysis[J].Oncogene,2016,35(15):1926-1942.
[15]Guo Q,Yuan Y,Jin Z,et al.Association between tumor vasculogenic mimicry and the poor prognosis of gastric cancer in China:an updated systematic review and metaanalysis[J].Biomed Res Int,2016,2016(4):1-8.
[2]Rao MR,Gopinath S,Alapati K,et al.Knockdown of cathepsin B and uPAR inhibits CD151 andα3β1 integrin-mediated cell adhesion and invasion in glioma[J].Mol Carcinog,2013,52(10):777-790.
[3]Wang Y,Han R,Zuo Z.Dexmedetomidine post-treatment induces neuroprotection via activation of extracellular signal-regulated kinase in rats with subarachnoid haemorrhage[J].Br J Anaesth,2016,116(3):384-392.
[4]Kovalska M,Kovalska L,Pavlikova M,et al.Intracellular signaling MAPK pathway after cerebral ischemia-reperfusion injury[J].Neurochem Res,2012,37(7):1568-1577.
[5]Zhao WJ,Yang YP.The formation of tumor vascular diversity and Its significance[J].Journal of Chinese Oncology,2015,21(6):507-511.[赵文静,杨俐萍.肿瘤血管多样性的形成及其研究意义[J].肿瘤学杂志,2015,21(6):507-511.]
[6]Liu X,Wang JH,Li S,et al.Histone deacetylase 3 expression correlates with vasculogenic mimicry through the phosphoinositide3-kinase/ERK-MMP-laminin5γ2 signaling pathway[J].Cancer Sci,2015,106(7):857-866.
[7]Wei Q,Liu ZX,Huang XL.Progress in the research of pro-angiogenesis of four transmembrane superfamily protein CD151[J].Chinese Journal of Histochemistry and Cytochemistry,2011,20(1):92-97.[魏全,刘正湘,黄晓琳.四跨膜超家族蛋白CD151促血管生成的研究进展[J].中国组织化学与细胞化学杂志,2011,20(1):92-97.]
[8]Baranski Z,Booij TH,Kuijjer ML,et al.MEK inhibition induces apoptosis in osteosarcoma cells with constitutive ERK1/2 phosphorylation[J].Genes Cancer,2015,6(11-12):503-512.
[9]Zuo HJ,Lin JY,Liu ZY,et al.Activation of the ERK signaling pathway is involved in CD151-induced angiogenic effects on the formation of CD151-integrin complexes[J].Chinese Pharmacology,2010,31(7):805-812.
[10]Bai J,Xu ZJ,Liao CL,et al.Progress in research on the vascularization mimicry in cancer[J].Journal of Central South University(Medical Science),2017,42(3):357-364.[白驹,徐志杰,廖朝亮,等.血管形成拟态在肿瘤中的研究进展[J].中南大学学报(医学版),2017,42(3):357-364.]
[11]Zhang X,Song Q,Wei C,et al.LRIG1 inhibits hypoxiainduced vasculogenic mimicry formation via suppression of the EGFR/PI3K/AKT pathway and epithelial-to-mesenchymal transitionin human glioma SHG-44 cells[J].Cell Stress Chaperones,2015,20(4):631-641.
[12]Lu XS,Sun W,Ge CY,et al.Contribution of the PI3K/MMPs/Ln-5γ2 andEphA2/FAK/Paxillin signaling pathways to tumor growth and vasculogenic mimicry of gallbladder carcinomas[J].Int J Oncol,2013,42(6):2103-2115.
[13]Zuo H,Liu Z,Liu X,et al.CD151 gene delivery after myocardial infarction promotes functional neovascularization and activates FAK signaling[J].Mol Med,2009,15(9-10):307-315.
[14]Zhang J,Gao Q,Zhou Y,et al.Focal adhesion kinase-promoted tumor glucose metabolism is associated with a shift of mitochondrial respiration to glycolysis[J].Oncogene,2016,35(15):1926-1942.
[15]Guo Q,Yuan Y,Jin Z,et al.Association between tumor vasculogenic mimicry and the poor prognosis of gastric cancer in China:an updated systematic review and metaanalysis[J].Biomed Res Int,2016,2016(4):1-8.