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肝细胞癌患者血浆基质金属蛋白酶的检测及临床意义
Determination and clinical significance of plasma matrix metalloproteinase in patients with hepatocellular carcinoma
文章发布日期:2019年03月07日  来源:  作者:张洪海,孙玉,刘芳,等  点击次数:310次  下载次数:66次

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【摘要】:目的探讨基质金属蛋白酶(MMPs)在肝细胞癌(HCC)患者中的表达水平及其与临床病理学特征的关系。方法选取2015年10月-2018年5月在首都医科大学附属北京佑安医院住院治疗的患者131例,其中乙型肝炎肝硬化患者35例,HCC患者96例;另选取同期门诊体检的健康对照者20例;采用悬浮液相芯片技术检测患者治疗前血浆MMP-1、MMP-2、MMP-7、MMP-9、MMP-10水平。非正态分布的计量资料2组间比较采用Mann-Whitney U检验,3组间比较采用Kruskal-Wallis H检验,进一步两两比较采用Dunn-Bonferroni检验,2组样本的相关性检验采用Spearman相关分析。结果HCC患者血浆MMP-1水平为813484(6147.94~11 148.47) pg/ml、MMP-7水平为6541.58(3906.63~9033.12) pg/ml,均高于肝炎肝硬化组及健康对照组,差异均有统计学意义(χ2值分别为23.521、66.112, P值均<0.001);HCC患者血浆MMP-2水平为103 774.45(90 485.91~123 673.90) pg/ml,高于健康对照组,差异有统计学意义(P<0.05)。肿瘤直径≥5 cm、伴有远处转移、合并门静脉侵犯、临床分期Ⅲ/Ⅳ期或病理ES Ⅲ/Ⅳ级组患者血浆MMP-1水平分别高于肿瘤直径<5 cm(Z=-7.313, P<0.001)、无远处转移(Z=-6.569, P<0.001)、无门静脉侵犯(Z=-6.051, P<0.001)、临床分期Ⅰ/Ⅱ期(Z=-5.844, P<0001)、病理ES Ⅰ/Ⅱ级组(Z=-7.423, P<0.001)患者, 差异均有统计学意义。伴有远处转移、合并门静脉侵犯、临床分期Ⅲ/Ⅳ期、病理ES Ⅲ/Ⅳ级组患者血浆MMP-7水平分别高于无远处转移(Z=-3.454, P=0.001 )、无门静脉侵犯(Z=-3.846, P<0.001)、临床分期Ⅰ/Ⅱ期(Z=-2.285, P=0.022)、病理ESⅠ/Ⅱ级组(Z=-3.287, P=0.001 )患者,差异均有统计学意义。结论HCC患者MMP-1和 MMP-7的表达与HCC转移、门静脉侵犯、临床分期及病理学分级相关,可协助判断HCC患者的肿瘤侵袭严重程度及预后。
【Abstract】:ObjectiveTo investigate the expression of matrix metalloproteinases (MMPs) in patients with hepatocellular carcinoma (HCC) and its association with clinicopathological features. MethodsA total of 131 patients who were hospitalized and treated in Beijing YouAn hospital from October 2015 to May 2018 were enrolled, and among these patients, 35 had hepatitis B cirrhosis and 96 had HCC. A total of 20 healthy controls who underwent physical examination at the outpatient service during the same period of time were enrolled as healthy control group. Suspension phase chip technology was used to measure the plasma levels of MMP-1, MMP-2, MMP-7, MMP-9, and MMP-10 before treatment. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between three groups; the Spearman correlation analysis was performed to investigate correlation. ResultsThe HCC group had a plasma level of MMP-1 of 8134.84 (6147.94-11 148.47) pg/ml and a plasma level of MMP-7 of 6541.58 (3906.63-9033.12) pg/ml, which were significantly higher than the plasma levels of MMP-1 and MMP-7 in the hepatitis B cirrhosis group and the healthy control group (χ2=23.521 and 66.112, both P<0.001). The HCC group had a plasma level of MMP-2 of 103 774.45 (90 485.91-123 673.90) pg/ml, which was significantly higher than that in the healthy control group (P<0.05). The patients with a tumor diameter of ≥5 cm, distant metastasis, portal venous invasion, clinical stage Ⅲ/Ⅳ, or Edmondson-Steiner (ES) grade Ⅲ/Ⅳ had a significantly higher plasma level of MMP-1 than those with a tumor diameter of <5 cm (Z=-7.313, P<0.001), without distant metastasis (Z=-6.569, P<0.001), without portal venous invasion (Z=-6.051, P<0.001), with clinical stage Ⅰ/Ⅱ(Z=-5.844, P<0.001), or with ES grade Ⅰ/Ⅱ (Z=-7.423, P<0.001). The patients with distant metastasis, portal venous invasion, clinical stage Ⅲ/Ⅳ, or ES grade Ⅲ/Ⅳ had a significantly higher plasma level of MMP-7 than those without distant metastasis (Z=-3.454, P=0.001), without portal venous invasion (Z=-3.846, P<0.001), with clinical stage Ⅰ/Ⅱ(Z=-2.285, P=0.022), or with ES grade Ⅰ/Ⅱ(Z=-3.287, P=0.001). ConclusionThe expression of MMP-1 and MMP-7 in HCC patients is associated with HCC metastasis, portal venous invasion, clinical stage, and pathological grade and can help to evaluate the severity and prognosis of tumor invasion in HCC patients.
【关键字】:癌, 肝细胞; 肝硬化; 基质金属蛋白酶类
【Key words】:carcinoma, hepatocellular; liver cirrhosis;matrix metalloproteinase
【引证本文】:ZHANG HH, SUN Y, LIU F, et al. Determination and clinical significance of plasma matrix metalloproteinase in patients with hepatocellular carcinoma[J]. J Clin Hepatol, 2019, 35(4): 825-829. (in Chinese)
张洪海, 孙玉, 刘芳, 等. 肝细胞癌患者血浆基质金属蛋白酶的检测及临床意义[J]. 临床肝胆病杂志, 2019, 35(4): 825-829.

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