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MUC5B、MMP-9在胆管癌中的表达及临床价值分析OA

Expression and clinical value analysis of MUC5B and MMP-9 in cholangiocarcinoma

中文摘要英文摘要

目的 探讨黏蛋白 5B(MUC5B)、基质金属蛋白酶-9(MMP-9)在胆管癌患者中的表达水平及其与患者临床特征、预后的关系,并分析其临床应用价值.方法 回顾性收集2022 年3 月—2023 年10 月于邯郸市第一医院诊治且完成随访的胆管癌患者 160 例临床资料,根据随访是否出现终点事件分为预后良好组(n=59)与预后不良组(n=101).比较癌组织与癌旁组织 MUC5B、MMP-9 表达水平差异,以及不同临床特征胆管癌患者癌组织 MUC5B、MMP-9表达水平差异.采用 COX 回归模型分析胆管癌患者预后情况的影响因素.建立 ROC 曲线分析 MUC5B、MMP-9表达对胆管癌患者预后的预测价值.结果 胆管癌癌组织 MUC5B、MMP-9 表达水平均高于癌旁组织(t/P=26.193/<0.001,24.772/<0.001).有胆管癌家族史、分化程度低、浸润深度在黏膜下层、肿瘤直径>3 cm、病理分期Ⅲ~Ⅳ期、淋巴结转移的胆管癌患者癌组织 MUC5B、MMP-9表达水平高于无胆管癌家族史、分化程度中高、浸润深度在黏膜层、肿瘤直径≤3 cm、病理分期Ⅰ~Ⅱ期、无淋巴结转移患者(MUC5B:t/P=3.946/<0.001,2.924/0.004,3.203/0.002,5.155/<0.001,2.816/0.005,4.576/<0.001;MMP-9:t/P=3.348/<0.001,2.865/<0.001,4.642/<0.001,6.069/<0.001,3.062/0.003,4.365/<0.001).Spearson 相关分析显示,MUC5B、MMP-9 与胆管癌家族史、浸润深度、肿瘤直径、病理分期、淋巴结转移呈正相关(MUC5B:rs/P=0.282/<0.001,0.241/0.002,0.374/<0.001,0.216/0.006,0.340/<0.001;MMP-9:rs/P=0.241/0.002,0.329/<0.001,0.434/<0.001,0.218/0.006,0.324/<0.001),与分化程度呈负相关(rs/P=-0.227/0.004,-0.200/0.011).160 例胆管癌患者中出现终点事件 101 例(63.13%).多因素 COX 回归分析显示,肿瘤直径>3 cm、病理分期Ⅲ~Ⅳ期、MUC5B 升高、MMP-9 升高为胆管癌患者预后不良的独立危险因素[HR(95%CI)=2.099(1.298~3.395),1.771(1.113~2.819),1.041(1.014~1.068),1.037(1.009~1.066),P<0.05].MUC5B、MMP-9 及二者联合的 AUC 分别为 0.879、0.886、0.922,敏感度分别为 0.772、0.752、0.881,特异度分别为 0.831、0.898、0.797.结论 MUC5B、MMP-9在胆管癌患者中均呈高表达,与胆管癌家族史、分化程度、浸润深度、肿瘤直径、病理分期、淋巴结转移等存在关联.MUC5B 升高、MMP-9升高为胆管癌患者预后不良的独立危险因素,二者联合对胆管癌患者预后有较好预测价值.

Objective To investigate the expression levels of mucin 5B(MUC5B)and matrix metalloproteinase-9(MMP-9)in patients with cholangiocarcinoma,analyze their relationship with the clinical characteristics and prognosis of the patients,and explore their clinical application value.Methods The clinical data of 160 patients with cholangiocarcinoma who were diagnosed and treated in our hospital and completed follow-up from March 2022 to October 2023 were retrospectively collected.The expression levels of MUC5B and MMP-9 were compared between cancer tissues and adjacent tissues,and were also compared among patients with different clinical characteristics.The COX regression model was used to analyze the factors influencing the prognosis of cholangiocarcinoma patients.The ROC curve was established to analyze the predictive va-lue of MUC5B and MMP-9 expression for the prognosis of cholangiocarcinoma patients.Results The expression levels of MUC5B and MMP-9 in cancer tissues were significantly higher than those in adjacent tissues(t/P=26.193/<0.001,24.772/<0.001).The expression levels of MUC5B and MMP-9 in cancer tissues were significantly higher in patients with a family his-tory,low differentiation,submucosal infiltration,tumor diameter>3 cm,pathological stage Ⅲ-Ⅳ,and lymph node metastasis than in those without a family history,with moderate to high differentiation,mucosal infiltration,tumor diameter≤3 cm,path-ological stage Ⅰ-Ⅱ,and without lymph node metastasis(MUC5B:t/P=3.946/<0.001,2.924/0.004,3.203/0.002,5.155/<0.001,2.816/0.005,4.576/<0.001;MMP-9:t/P=3.348/<0.001,2.865/<0.001,4.642/<0.001,6.069/<0.001,3.062/0.003,4.365/<0.001).Spearman correlation analysis showed that MUC5B and MMP-9 were significantly positively correlated with family history,infiltration depth,tumor diameter,pathological stage,and lymph node metastasis(MUC5B:rs/P=0.282/<0.001,0.241/0.002,0.374/<0.001,0.216/0.006,0.340/<0.001;MMP-9:rs/P=0.241/0.002,0.329/<0.001,0.434/<0.001,0.218/0.006,0.324/<0.001),and significantly negatively correlated with differentiation degree(P<0.01).Follow-up results showed that 101 out of 160 cholangiocarcinoma patients had endpoint events,with an incidence rate of 63.13%.Based on the occurrence of endpoint events,patients were divided into a favorable prognosis group(n=59)and an unfavorable prognosis group(n=101).Multiva-riate COX regression analysis showed that tumor diameter>3 cm,pathological stage Ⅲ-Ⅳ,elevated MUC5B,and elevated MMP-9 were independent risk factors for poor prognosis in cholangiocarcinoma patients(all P<0.05).Using the Cut-off value as the standard,the AUCs of MUC5B,MMP-9,and their combination were 0.879,0.886,and 0.922,respectively.At the Cut-off value,the sensitivities of MUC5B,MMP-9,and their combination were 0.772,0.752,and 0.881,respectively;the specificities were 0.831,0.898,and 0.797,respectively.Conclusion Both MUC5B and MMP-9 are highly expressed in patients with cholangiocarcinoma,and are associated with family history,differentiation degree,infiltration depth,tumor diameter,pathological stage,and lymph node metastasis.Tumor diameter>3 cm,pathological stage Ⅲ-Ⅳ,elevated MUC5B,and elevated MMP-9 are independent risk factors for poor prognosis.MUC5B and MMP-9 demonstrate good pre-dictive value for the prognosis of cholangiocarcinoma patients,and their combined use can improve the sensitivity of auxilia-ry diagnosis.

张伍杰;李红磊;谢亚玎;张会娟;谭诚

056002 河北邯郸,邯郸市第一医院肝胆外二科056002 河北邯郸,邯郸市第一医院肝胆外二科056002 河北邯郸,邯郸市第一医院肝胆外二科056002 河北邯郸,邯郸市第一医院肝胆外二科056002 河北邯郸,邯郸市第一医院肝胆外二科

医药卫生

胆管癌黏蛋白5B基质金属蛋白酶-9病理特征预后预测

CholangiocarcinomaMucin 5BMatrix metalloproteinase-9Pathological featuresPrognosis prediction

《疑难病杂志》 2026 (9)

1075-1080,6

河北省医学科学研究课题计划资助项目(20220483) Medical Research Project Plan of Hebei Province(20220483)

10.3969/j.issn.1671-6450.2026.09.009

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