【摘要】 背景:胆管癌是起源于胆管上皮细胞、恶性程度极高的消化系统肿瘤。Claudin-4是细胞间紧密连接结构的关键组分,上皮肿瘤中普遍存在claudin-4表达异常,并与肿瘤发生、发展有密切联系。目的:分析claudin-4在胆管癌中的表达及其与患者临床病理特征和预后的相关性。方法:应用免疫组化方法检测claudin-4在77例胆管癌及其配对癌旁组织中的表达率和表达强度,分析其表达与患者临床病理特征的关系,同时以Kaplan-Meier生存曲线行生存分析。结果:胆管癌组织中claudin-4以强阳性表达为主,癌旁组织以中等和弱阳性表达为主,癌组织免疫组化评分显著高于癌旁组织(9.22±3.62对7.12±4.26,P<0.05)。胆管癌组织中的claudin-4表达与肿瘤部位和分化程度显著相关(P均<0.05),低分化腺癌高表达率显著高于高-中分化腺癌(76.2%对50.0%)。Claudin-4低表达组和高表达组31个月累积生存率分别为29.8%和21.1%,组间差异无统计学意义(P>0.05)。结论:Claudin-4在胆管癌中呈异常高表达,并与肿瘤分化程度呈负相关,因此有望成为胆管癌诊断新的生物学标记物和治疗靶点。更多还原

【Abstract】 Background: Cholangiocarcinoma( CCA) is a fatal digestive system tumor arising from biliary epithelium. Claudin-4,a key constituent of intercellular tight junction,is aberrantly and widely expressed in various epithelial tumors,and is correlated with tumorigenesis and tumor progression. Aims: To investigate the expression of claudin-4 in CCA and its correlation with clinicopathological characteristics of the tumor and patient’s prognosis. Methods: Immunohistochemistry was used to determine the expression rate and intensity of claudin-4 in CCA tissue and matched paracancerous tissue of 77 CCA patients. Correlation of claudin-4 expression in CCA with its clinicopathological characteristics was analyzed,and survival analysis was conducted by using Kaplan-Meier method. Results: Claudin-4 was strongly expressed in CCA tissue and mildly or weakly expressed in matched paracancerous tissue; the immunohistochemical score was significantly higher in cancerous tissue than in paracancerous tissue( 9. 22 ± 3. 62 vs. 7. 12 ± 4. 26,P < 0. 05). Claudin-4 expression was significantly correlated with tumor location and tumor differentiation( P all < 0. 05); the high expression rate was significantly higher in poorly differentiated CCA than in well or moderately differentiated ones( 76. 2% vs. 50. 0%). The31-month accumulate survival rates of claudin-4 low-expression group and high-expression group were 29. 8% and 21. 1%,respectively( P > 0. 05). Conclusions: Claudin-4 is highly expressed in CCA and negatively correlated with tumor differentiation. It might be a novel diagnostic biomarker and therapeutic target for CCA.更多还原