结直肠癌ADAMs表达谱及其ADAM-28的表达及意义

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

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。

Objective 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 eolorectal 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. Immunohis- tochemistry showed that the positive rate of ADAM-28 in coloreetal 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.