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ICAM-1、MMP-9及NF-κB在胆管癌中的表达及与外周血免疫抑制细胞的关系

Expression of ICAM-1,MMP-9 and NF-κB in Cholangiocarcinoma and Their Relationship with Immunosuppressive Cells in Peripheral Blood
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摘要 目的探讨细胞间粘附分子-1(ICAM-1)、基质金属蛋白酶-9(MMP-9)及NF-κB在胆管癌中的表达及外周血中CD14^(+)CD11b^(+)HAL-DR^(-)髓源性抑制细胞(MDSC)的关系。方法选取昆明医科大学附属甘美医院2017年12月至2019年12月收治的胆管癌患者60例研究对象。采用免疫组化法测定胆管癌组织与癌旁正常组织ICAM-1蛋白、MMP-9蛋白及NF-κB蛋白;采用流式细胞术检测患者外周血中CD14^(+)CD11b^(+)HAL-DRMDSC比例。比较胆管癌组织与癌旁组织ICAM-1蛋白、MMP-9蛋白和NF-κB蛋白表达;不同病理特征ICAM-1蛋白、MMP-9蛋白和NF-κB蛋白表达及外周血中CD14^(+)CD11b^(+)HAL-DR^(-)MDSC比例;ICAM-1蛋白、MMP-9蛋白和NF-κB蛋白表达与外周血中CD14^(+)CD11b^(+)HAL-DR^(-)MDSC比例相关性。结果胆管癌组织ICAM-1蛋白、MMP-9蛋白和NF-κB蛋白表达阳性率均高于癌旁正常组(P<0.05)。不同性别、年龄、病理分级和淋巴结转移ICAM-1蛋白表达比较无明显差异(P>0.05);III~IV期ICAM-1蛋白表达阳性率高于I~II期(P<0.05)。不同性别、年龄、病理分级和临床分期MMP-9蛋白表达比较无明显差异(P>0.05);淋巴结转移MMP-9蛋白表达阳性率高于无淋巴结转移(P<0.05)。不同性别、年龄、病理分级和淋巴结转移NF-κB蛋白表达比较无明显差异(P>0.05);III~IV期NF-κB蛋白表达阳性率高于I~II期(P<0.05)。不同性别、年龄、病理分级和淋巴结转移CD14^(+)CD11b^(+)HAL-DR^(-)MDSC比例比较无明显差异(P>0.05);III~IV期CD14^(+)CD11b^(+)HAL-DR^(-)MDSC比例高于I~II期(P<0.05)。ICAM-1蛋白、MMP-9蛋白及NF-κB蛋白表达与CD14^(+)CD11b^(+)HAL-DR^(-)MDSC比例呈线性正相关。结论ICAM-1蛋白、MMP-9蛋白及NF-κB蛋白表在胆管癌中高表达,外周血中CD14^(+)CD11b^(+)HAL-DR^(-)MDSC比例升高,且ICAM-1蛋白、MMP-9蛋白及NF-κB蛋白表达与CD14^(+)CD11b^(+)HAL-DR^(-)MDSC比例呈线性正相关。 Objective To investigate the expression of intercellular adhesion molecule-1(ICAM-1),matrix metalloproteinase-9(MMP-9)and NF-κB in cholangiocarcinoma and the relationship between CD14^(+)CD11b^(+)HAL-DR^(-)MDSC in peripheral blood.Methods From December 2018 to December 2019,60 patients with cholangiocarcinoma were selected.Immunohistochemistry was used to detect ICAM-1 protein,MMP-9 protein and NF-κB protein in cholangiocarcinoma and adjacent normal tissues,and flow cytometry was used to detect the ratio of CD14^(+)CD11b^(+)HAL-DR^(-)MDSC in patients’peripheral blood.The expression of ICAM-1 protein,MMP-9 protein and NF-κB protein in cholangiocarcinoma and adjacent tissues were compared;the expression of ICAM-1 protein,MMP-9 protein and NF-κB protein in different pathological features and the ratio of CD14^(+)CD11b^(+)HAL-DR^(-)MDSC in peripheral blood were compared;the expression of ICAM-1 protein,MMP-9 protein and NF-κB protein was correlated with the ratio of CD14^(+)CD11b^(+)HAL-DR^(-)MDSC in peripheral blood.Results The positive rates of ICAM-1 protein,MMP-9 protein and NF-κB protein in cholangiocarcinoma were higher than those in normal group(P<0.05).There was no significant difference in the expression of ICAM-1 protein in different gender,age,pathological grade and lymph node metastasis(P>0.05);the positive rate of ICAM-1 protein expression in stage III-IV was higher than that in stage I-II(P<0.05).There was no significant difference in the expression of MMP-9 between different genders,ages,pathological grades and clinical stages(P>0.05);the positive rate of MMP-9 in lymph node metastasis was higher than that in non lymph node metastasis(P<0.05).There was no significant difference in the expression of NF-κB protein between different genders,ages,pathological grades and lymph node metastasis(P>0.05);the positive rate of NF-κB protein expression in stage III-IV was higher than that in stage I-II(P<0.05).There was no significant difference in the proportion of CD14^(+)CD11b^(+)HAL-DR^(-)MDSC in different sex,age,pathological grade and lymph node metastasis(P>0.05);the proportion of CD14^(+)CD11b^(+)HAL-DR^(-)MDSC in stage III-IV was higher than that in stage I-II(P<0.05).The expression of ICAM-1,MMP-9 and NF-κB was positively correlated with the ratio of CD14^(+)CD11b^(+)HAL-DR^(-)MDSC.Conclusion ICAM-1 protein,MMP-9 protein and NF-κB protein are highly expressed in cholangiocarcinoma,the ratio of CD14^(+)CD11b^(+)HAL-DR^(-)MDSC in peripheral blood is increased,and the expression of ICAM-1 protein,MMP-9 protein and NF-κB protein is positively correlated with the ratio of CD14^(+)CD11b^(+)HAL-DR^(-)MDSC.
作者 李志强 高红强 李镜锋 余杰琦 王冬冬 陈刚 褚光 LI Zhi-qiang;GAO Hong-qiang;LI Jing-feng;YU Jie-qi;WANG Dong-dong;CHEN Gang;CHU Guang(Dept.of Hepatobiliary and Pancreatic Surgery,The Calmette Affiliated Hospital of Kunming Medical University,Kunming Yunnan 650224,China)
出处 《昆明医科大学学报》 CAS 2021年第11期93-98,共6页 Journal of Kunming Medical University
基金 云南省科技厅科技计划项目(2018FH001-072)。
关键词 细胞间粘附分子-1 基质金属蛋白酶-9 NF-ΚB 胆管癌 CD14^(+)CD11b^(+)HAL-DR^(−)髓源性抑制细胞 Intercellular adhesion molecule-1 Matrix metalloproteinase-9 NF-κB Cholangio-carcinoma CD14^(+)CD11b^(+)HAL-DR^(−)myelogenous suppressor cell
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