陈茹　苏小青　潘升华　陈了之　周静　黄益灯

[摘要] 目的 探討紧密连接蛋白claudin-3、claudin-7在鼻咽癌患者组织中的表达及临床意义。 方法 收集2014年1月～2016年1月温州医科大学附属第三医院病理科鼻咽癌患者存档蜡块标本52例作为研究对象，同时选择鼻咽黏膜正常组织20例作为对照。使用免疫组学方法检测不同鼻咽癌组织中紧密连接蛋白claudin-3、claudin-7表达情况，分析其与患者临床病理参数的关系，分析鼻咽癌组织中紧密连接蛋白claudin-3、claudin-7表达程度的相关性。 结果 鼻咽癌组织中紧密连接蛋白claudin-3阳性表达率（51.92%）与正常鼻咽黏膜组织（45.00%）比较，差异无统计学意义（P > 0.05）。而鼻咽癌组织中紧密连接蛋白claudin-7阳性表达率（26.92%）与正常鼻咽黏膜组织（55.00%）比较，差异有统计学意义（P = 0.025）。claudin-3的阳性表达率在鼻咽癌Ⅲ+Ⅳ期患者中明显高于Ⅰ+Ⅱ期患者（P = 0.002）。与紧密连接蛋白claudin-7在不伴淋巴结转移的鼻咽癌组织中的表达（9/15）比较，伴有淋巴结转移的鼻咽癌组织中的阳性表达（5/37）明显降低（P = 0.001）。相关性分析结果显示，紧密连接蛋白claudin-3和claudin-7无明显相关性（r = 0.2696，P = 0.0532）。 结论 claudin-3与肿瘤TNM分期有关，考虑其在鼻咽癌的发展中可能起一定的作用。claudin-7表达下调可能在鼻咽癌的发生、转移中发挥一定的作用，紧密连接蛋白claudin-3和claudin-7有望成为治疗鼻咽癌的新靶点。

[关键词] claudin-3；claudin-7；鼻咽癌；VCA-IgA；免疫组化

[中图分类号] R739 [文献标识码] A [文章编号] 1673-7210（2018）11（b）-0101-05

[Abstract] Objective To explore the expression of claudin-3， claudin-7 in patients with nasopharyngeal carcinoma（NPC） and to analyze the relationship between the proteins and clinical significance. Methods Fifty-two archival paraffin embedded tissue specimens of nasopharyngeal were retrospectively analyzed from January 2014 to January 2016 at the Third Affiliated Hospital of Wenzhou Medical University. Another 20 samples of Histologically normal nasopharyngeal tissues were also obtained as control group. Immunohistochemstry was used to detect the expression of claudin-3 and claudin-7 in the different tissues， and the relationship was analyzed between the expression and clinic pathological parameter. The relationship of the expression levels of claudin-3 and claudin-7 in nasopharyngeal carcinoma tissues was analyzed. Results There was no statistically significant difference in the positive expression rate of claudin-3 （51.92%） between nasopharyngeal carcinoma and adjacent non-neoplastic tissues （45.00%） （P > 0.05）. While the positive expression rate of claudin-7 in nasopharyngeal carcinomas （26.92%）， in comparison with the adjacent non-neoplastic tissues （55.00%）， there was significant difference （P = 0.025）. The positive expression rate of claudin-3 in the Ⅲ+Ⅳ stage patients was significantly higher than that in the Ⅰ+Ⅱ stage patients （P = 0.002）. Compared with the positive expression rate of claudin-7 in nasopharyngeal carcinomas without cervical lymph node metastasis （9/15）， the positive expression rate in nasopharyngeal carcinomas with cervical lymph node metastasis was remarkably lower （5/37） （P = 0.001）. Correlation analysis results showed that there was no relationship between expression of claudin-3 and claudin-7 （r = 0.2696， P = 0.0532）. Conclusion claudin-3 relates to the TNM tumor staging， in consideration of the effect in the nasopharyngeal carcinoma progress. claudin-7 decreased expression plays a role in the occurrence and development of nasopharyngeal carcinoma. claudin-3 and claudin-7 may be novel biomarkers for the new target for nasopharyngeal carcinoma treatment.

[Key words] claudin-3； claudin-7； Nasopharyngeal carcinoma； VCA-IgA； Immunohistochemistry

鼻咽癌的发生发展是一个多基因参与、多阶段变异累积形成的病理过程。寻找鼻咽癌的分子标志物将有利于鼻咽癌患者个体化治疗方案的选择及预后的评估。紧密连接蛋白是紧密连接的骨架蛋白[1]，参与紧密连接的形成及细胞间的信号转导。目……