VEGF和miR-205及靶蛋白Ezrin和LaminA/C在卵巢癌中的表达及意义

Expression and signii cance of VEGF, miR-205 and target protein Ezrin and Lamin A/C in ovarian cancer

目的:分析血管内皮生长因子(vascular endothelial growth factor,VEGF),miR-205,Ezrin,Lamin A/C在卵巢癌组织中的表达及意义。方法:采用酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)检测卵巢癌患者和正常女性血清中VEGF的含量;免疫组织化学检测上皮性卵巢癌组织、卵巢良性肿瘤组织和正常卵巢组织中血管内皮细胞生长因子受体-1(vascular endothelial cell growth factor receptor-1,VEGFR-1),VEGFR-2,Ezrin,Lamin A/C蛋白的表达情况和CD31所标记的微血管密度(microvessel density,MVD);采用荧光定量PCR方法检测卵巢上皮性癌组织、卵巢良性肿瘤组织和正常卵巢组织中miR-205,Ezrin和Lamin A/C的相对表达量。结果:VEGF在上皮性卵巢癌患者血清中的表达水平为(116.10±11.94),高于正常女性(40.04±4.97,P<0.05);VEGFR-1和VEGFR-2在卵巢上皮性癌组织中的阳性表达率分别为75.9%和91.4%,高于卵巢良性肿瘤组织和正常卵巢组织中的阳性表达率(P<0.05),VEGFR-1和VEGFR-2在卵巢良性肿瘤组织和正常卵巢组织中的表达差异无统计学意义(P>0.05);MVD在上皮性卵巢癌组织中的计数为(7.56±0.51),高于正常卵巢组织(1.22±0.56,P<0.05),MVD在卵巢良性肿瘤组织和正常卵巢组织中的表达差异无统计学意义(P>0.05);miR-205在上皮性卵巢癌组织中的相对表达量为(0.106±0.035),高于正常卵巢组织中的相对表达量(0.0007±0.0005,P<0.05),miR-205在卵巢良性肿瘤组织中的相对表达量为(0.0002±0.0003),高于正常卵巢癌组织中的相对表达量,但差异无统计学意义(P>0.05);免疫组织化学结果显示:Ezrin和Lamin A/C在上皮性卵巢癌组织中的阳性表达率分别为51.7%和60.3%,低于卵巢良性肿瘤组织和正常卵巢组织中的阳性表达率(P<0.05),Ezrin和Lamin A/C在卵巢良性肿瘤组织和正常卵巢组织中的表达差异无统计学意义(P>0.05);RT-PCR结果显示:Ezrin和Lamin A/C在上皮性卵巢癌组织中的相对表达量低于正常卵巢组织中的相对表达量(P<0.05);Ezrin和Lamin A/C在卵巢良性组织中的相对表达量高于在上皮性卵巢癌组织,但差异无统计学意义(P>0.05)。结论:VEGF在上皮性卵巢癌患者血清中表达上调;miR-205在上皮性卵巢癌组织中表达上调;差异蛋白Ezrin和Lamin A/C在上皮性卵巢癌组织中表达下调,提示VEGF和miR-205及靶蛋白Ezrin和Lamin A/C与卵巢癌的侵袭、转移相关。

Objective: To analyze the expression of vascular endothelial growth factor(VEGF), miR-205, Ezrinand Lamin A/C in ovarian cancer tissues. Methods: The expression of VEGF in the serum of epithelial ovarian cancer and that of healthy volunteers were detected by enzyme-linked immunosorbent assay; the expressions of vascular endothelial growth factor receptor 1(VEGFR-1), VEGFR-2, Ezrin and Lamin A/C were detected by immunohistochemistry and the micro-vessel density(MVD) of CD31 was detected by immunohistochemistry in epithelial ovarian cancer, benign ovarian and normal ovarian specimens; and the expression of miR-205, Ezrin and Lamin A/C were detected by real-time PCR in epithelial ovarian cancer, benign ovarian and normal ovarian specimens. Results: The expression of VEGF in the serum of epithelial ovarian cancer patients(116.10± 11.94) was signii cantly higher than that of healthy volunteers(40.04±4.97, P<0.05). h e positive expression rates of VEGFR-1 and VEGFR-2 in the epithelial ovarian cancer specimens were 75.9% and 91.4% respectively, which were significantly higher than that in the benign ovarian and the normal ovarian specimens(P<0.05). No differences were observed in the positive expression rates of VEGFR-1 and VEGFR-2 between the benign ovarian and the normal ovarian specimens(P>0.05). The average length of MVD in the epithelial ovarian cancer specimens(7.56±0.51), was signii cantly higher than that in the normal ovarian specimens(1.22±0.56, P<0.05) and in the benign ovarian specimens(0.7±0.39, P<0.05). No dif erences were observed in the average length of MVD between the benign ovarian and the normal ovarian specimens(P>0.05). The relative expression level of miR-205 was 0.106±0.035 in the epithelial ovarian cancer specimens, which was significantly higher than that in the normal ovarian specimens(0.0007±0.0005, P<0.05); the relative expression level of miR-205 in the benign ovarian specimens was(0.0002±0.0002), higher than that in the normal ovarian specimens, but with no signii cance(P>0.05). h e positive expression rates of Ezrin and Lamin A/C in the epithelial ovarian cancer specimens were 51.7% and 60.3%, respectively, which were signii cantly lower than those in the benign ovarian and the normal ovarian specimens(P<0.05). No dif erences were observed in the positive expression rates of Ezrin and Lamin A/C between the benign ovarian and the normal ovarian specimens(P>0.05). The relative expression levels of Ezrin and Lamin A/C mRNA in the epithelial ovarian cancer specimens were(0.026±0.003) and(0.060±0.007), respectively, which were signii cantly lower than those in the normal ovarian specimens(P<0.05). h ere was no statistical signii cance between the relative expression level of Ezrin and Lamin A/C mRNA in the epithelial ovarian cancer specimens and that in the benign ovarian specimens(0.029± 0.011, 0.089 ± 0.019; P>0.05). Conclusion: VEGF is significantly expressed in the serum of epithelial ovarian cancer patients; and miR-205 is up-regulated in the epithelial ovarian cancer specimens. Ezrin and Lamin A/C are down-regulated in the epithelial ovarian cancer samples. VEGF, miR-205 and target protein may be associated with the invasion and metastasis of epithelial ovarian cancer.