MMP-9,2,7及其抑制剂TIMP-1,2,3在卵巢肿瘤组织中的表达及临床意义

Expression of Matrix Metalloproteinases-9,2,7,and Tissue Inhibitor of Metalloproteinases-1,2,3 mRNA in Ovarian Tumors and Their Clinical Significance

背景与目的:基质金属蛋白酶(matrixmetalloproteinases,MMPs)通过降解细胞外基质在肿瘤的侵袭与转移中起着重要作用,MMPs活性又受到其抑制剂(tissueinhibitorofmatrixmetalloproteinase,TIMPs)的调节。本研究通过检测MMP-9、MMP-2、MMP-7及TIMP-1、TIMP-2、TIMP-3mRNA在卵巢肿瘤组织中的表达,探讨其与卵巢癌临床病理特征和预后的关系。方法:应用RT-PCR方法检测48例卵巢癌、21例良性肿瘤及22例正常卵巢组织中MMP-9、MMP-2、MMP-7及TIMP-1、TIMP-2、TIMP-3mRNA的表达。结果:MMP-9阳性率和MMP-9、MMP-2半定量值在卵巢癌组织中明显高于正常卵巢组织(P<0.05)。TIMP-2、MMP-7、TIMP-3在卵巢恶性及良性肿瘤组织中的阳性率及半定量值明显高于正常卵巢组织。MMP-9/TIMP-1在卵巢癌组织中的比值(0.91±0.67)明显高于正常卵巢组织(0.15±0.34)。MMP-9表达水平与卵巢癌的手术病理分期及预后有关,在Ⅲ～Ⅳ期患者中的表达(1.13±0.66)显著高于Ⅰ～Ⅱ期患者(0.60±0.54)(P<0.05);MMP-9其阳性患者平均生存时间为(43.00±17.12)个月,累积生存率为47.37%,明显低于MMP-9阴性者(100%)。结论:MMP-9、MMP-2、MMP-7、TIMP-2、TIMP-3基因在卵巢恶性肿瘤组织中的表达增加。

BACKGROUND &OBJECTIVE:Matrix metalloproteinases (MMPs) play an imp ortant role in cancer cell invasion,and metastasis by degrading the extracellula r matrix (ECM). The activities of MMPs are regulated by tissue inhibitor of meta lloproteinases (TIMPs). This study was to detect mRNA expression of MMP-9,2,7, and TIMP-1,2,3 in ovarian tumor tissues, and explore their correlations with cl inicopathologic characteristics,and prognosis of patients with ovarian cancer. M ETHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to a ssay the positive rates, and half-quantity values of MMP-9,2,7, and TIMP-1,2, 3 mRNA in 48 cases of malignant ovarian tumor tissues,21 cases of benign ovarian tumor tissues, and 22 cases of normal ovarian tissues. RESULTS: The positive ra te of MMP-9 mRNA, and the half-quantity values of MMP-9,MMP-2 were significa ntly higher in malignant tumor tissues than those in normal ovarian tissues (P< 0.05). The positive rates and half-quantity values of TIMP-2, MMP-7, TIMP-3 mRNA were significantly higher in malignant and benign ovarian tumor tissues tha n those in normal ovarian tissues(P< 0 05). The ratio of MMP-9/TIMP-1 was hig her in malignant ovarian tumor tissues(0.91±0.67) than that in normal ovarian t issues (0.14±0.33)(P< 0.05). The expression level of MMP-9 mRNA was higher in ovarian cancer tissues of stage Ⅲ-Ⅳ(1.13±0.66) than those of stageⅠ-Ⅱ(0.6 0±0.54)(P< 0.05). The mean survival time of MMP-9 positive patients was (43.00 ±17.12) months, and cumulate survival rate was 47.37%, significantly lower tha n that of MMP-9 negative patients (100%). CONCLUSIONS:MMP-9, MMP-2, MMP-7, TIMP-2, TIMP-3 are over-expressed in ovarian malignant tissues. The over-exp ression of MMP-9, and the imbalance between MMP-9 and TIMP-1 play important r oles in the progress of advanced ovarian cancer. MMP-9 may be a useful prognost ic marker for patients with advanced ovarian carcer.