临床肿瘤学杂志

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结直肠癌ADAMs表达谱及其ADAM-28的表达及意义

王金蒙,朱莉,王晶莹,李文峰,徐云升   

  1. 325000 浙江温州 温州医科大学第一附属医院皮肤科
  • 收稿日期:2016-11-30 修回日期:2017-04-20 出版日期:2017-08-31 发布日期:2017-08-31
  • 通讯作者: 徐云升

Expression profiles of ADAMs and clinical significance of ADAM-28 in colorectal carcinoma

WANG Jinmeng,ZHU Li,WANG Jingying,LI Wenfeng,XU Yunsheng   

  1. Department of Dermatovenereology,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China
  • Received:2016-11-30 Revised:2017-04-20 Online:2017-08-31 Published:2017-08-31
  • Contact: XU Yunsheng

摘要: 目的 探讨金属蛋白酶解离素(ADAMs)家族成员ADAM-8、ADAM-9、ADAM-10、ADAM-12、ADAM-15、ADAM-17、ADAM-19、ADAM-28、ADAM-33在结直肠癌中的表达分布,并分析ADAM-28表达与结直肠癌临床病理特征的关系及其对预后的影响。方法 实时荧光定量PCR(QPCR)检测6例新鲜结直肠癌组织和对应癌旁组织中ADAMs mRNA的表达,Western blotting 检测ADAM-28蛋白在上述样本中的表达。免疫组化法检测ADAM-28在218例结直肠癌组织中的表达,分析ADAM-28表达与临床病理特征和预后的关系。结果 ADAM-8、ADAM-9、ADAM-17、ADAM-28和ADAM-33 mRNAs在结直肠癌组织中表达升高,ADAM-12表达下调,ADAM-10、ADAM-15和ADAM-19无明显变化。ADAM-28蛋白表达在结直肠癌组织中也升高。免疫组化检测显示,结直肠癌组织中ADAM-28的阳性表达率为68.8%(150/218),其表达与淋巴结转移(P=0.032)、TNM分期(P=0.032)和分化程度(P=0.019)有关。ADAM-28阳性表达者的中位总生存时间(OS)明显劣于ADAM阴性表达者(36.75个月vs. 95.10个月),差异有统计学意义(P<0.001)。Cox多因素分析显示,ADAM-28是影响OS的独立因素(P<0.05)。结论 ADAM-28表达与结直肠癌的发生、发展密切相关,是潜在评估结直肠癌预后的预测因子。

Abstract: bjective To investigate the expression profiles of a disintegrin and metalloproteinases(ADAMs)family menbers ADAM-8,ADAM-9,ADAM-10,ADAM-12,ADAM-15,ADAM-17, ADAM-19,ADAM-28,ADAM-33 in colorectal carcinoma and to determine the clinical significance of ADAM-28 in colorectal carcinoma. Methods QPCR was used to detect the relative levels of ADAMs mRNA in colorectal carcinoma and matched non-cancerous tissues,and Western blotting was used to detected ADAM-28 protein expression. Immunohistochemistry was taken to analyze the expression of ADAM-28 in 218 colorectal carcinoma samples and its correlation with clinicopathological variables was then analyzed. Results The mRNAs expression of ADAM-8, ADAM-9, ADAM-17, ADAM-28 and ADAM-33 were up-regulated in colorectal carcinoma, ADAM-12 mRNA was down-regulated, and while the mRNAs of ADAM-10, ADAM-15 and ADAM-19 had no obvious changes. ADAM-28 protein was up-regulated in colorectal carcinoma. Immunohistochemistry showed that the positive rate of ADAM-28 in colorectal carcinoma tissues was 68.8%(150/218). The expression of ADAM-28 significantly correlated with regional lymph node metastasis, differentiation and TNM stage(P<0.05). Survival analysis revealed that patients with positive ADAM-28 expression had a shorter median overall survival than those of ADAM-28 negative expression(36.75 months vs.95.10 months, P<0.001). Cox multi-factors analysis showed that ADAM-28 was an independent factor influencing overall survival(P<0.05). Conclusion ADAM-28 contributes to the occurrence and development of colorectal carcinoma;ADAM-28 may be served as a potential biomarker in predicting patients' outcome.

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