| Ovarian cancer is one of the most common malignant tumors in gynecology, the incidence rate is lower than cervical cancer and endomentrial cancer,but it has the highest malignancy in gynecological oncology.Since lack of effective early diagnosis index,most of ovarain cancer have been diagnosied on moderat or late stage, it has the most mortality in gynecological oncology. Although many research from domestic and foreign about ovarian cancer have been published, its etiology and pathogenesis are not clear yet. At the early stage,Ovarian cancer lacks typical symptoms and early diagnosis,therefore 70% of patients are finally diagnosed with ascites, distant metastasis and other advanced symptoms. In present, although the surgery and chemotherapy improve the life quality of patients with advanced ovarian cancer significantly, the overall 5-year survival rate is just around 30%. Currently, the ovarian cancer has become a serious threat to women’s life. Most of Ovarian cancer are originated in ovarian epithelial tissue.75%～90% of ovarian cancer patients was epithelial ovarian cancer(EOC).To investigate the mechanism of carcinogenesis and development about EOC, looking for effective biomarkers and therapeutic targets and improving the prognosis are the most important targets in the ovarian cancer research.miRNAs are recently found which is a class of small non-coding RNAs of 21-25 nucleotides.Through imperfect pairing with 3’-UTR of target messenger RNAs (mRNAs) cause targeted RNA translational repression or mRNA decay.miRNAs canparticipant in the regulation of cellular growth differentiation, energy metabolism, apoptosis and other important cellular physiological processes. Recent study show that microRNA has closely related with the carcinogenesis,development, metastasis and prognosis of many malignant tumors. However,miR-126 is down-regulated in many tumors, it may play a role of suppressing tumor in carcinogenesis,which has few researches and different opinions on ovarian cancer. EGFL7 is a secreted protein specifically expressed by endothelial cells in normal tissues and overexpressed by cancer cells in various human solid tumors. But there has few studies about EGFL7 expression and effect on ovarian cancer. miR-126 is located within the 7th intron of EGFL7, meanwhile in many studies of NSCLC,prostatic cancer and other cancer suggest that EGFL7 is also one of the major targets of miR-126. Thus,we investigate the expression of miR-126 and EGFL7 in epithelial ovarian cancer, and explore the relation among miR-126,EGFL7 and MVD to discuss how miR-126 and EGFL7 play a role in mechanism of epithelial ovarian cancer development, expecting to look for the early diagnose theory basis, the prognosis and therapy of EOC.ObjectiveTo investigate the expression of miR-126,EGFL7 and MVD in different ovarian epithelial tissues,and to analysis the relationship among them in EOC. And to discuss the significance of them in occurrence and development of EOC.Materials and methods1. Study objects 89 cases of surgical specimens collected from the pathology department of The First and Third Affiliated Hospital of Zhengzhou University from March 2010 to August 2014. All of specimens are pathologically confirmed including 45 cases of EOC tissues(Malignant Group:12 cases of FIGO Ⅰ-Ⅱ,33 cases of FIGO III-IV; 25 cases of high histological grade,11 cases of median histological grade,9 cases of low histological grade;29 cases of serous cystadenocarcinoma,8 cases of mucinous cystadenocarcinoma,4 cases of endometrioid carcinoma and 4 cases of clear cell carcinoma; 31 cases have LN metastasis,14 cases haven’t LN metastasis), 23 cases of benign epithelial ovarian neoplasms tissues and 21 cases of normal tissues(Normal Group:because of benign uterine disease,the adnexa have been surgical resected). Malignant Group had not received the preoperative radiotherapy or chemotherapy. The age of all ranged from 27 to 73 years,the average age is 47.6±5.5 years. Surgical specimens have been took after the approval of Ethics Committee and enrolled patients.2. Methods Immunohistochemical method was used to detect the protein expression of EGFL7 and CD34(represent MVD) in 89 cases of epithelial ovarian tissues. qRT-PCR method was used to detect the mRNA expression of miR-126 in 89 cases of epithelial ovarian ti ssues and the mRNA expression of EGFL7 in 45 cases of epithelial ovarian tumor tissues.3. Statistics approach SPSS 19.0 was used to deal with the data. The expression of miR-126 evaluated by M(P25-P75),Kruskal-Wallis test was used to deal with this data, Nemeyi method was used to compare the expression of miR-126 in different epithelial ovarian tissues. Other data were evaluated by x±s.Chi-square test and one-way ANOVA were used to compare the protein expression of EGFL7 and CD34(MVD) in different epithelial ovarian tissues, respectively. Indenpent-sam ple test and one-way ANOVA were used to compare different clinical pathological features of EOC with the expression of miR-126 mRNA,EGFL7 mRNA and MVD.The correlation among the three factors was assessed by Spearman rank correlation and Pearson Correlation. Significant level a=0.05, the comparision between two groups, significant level α’=α/comparision times=0.0167.Results1. The expression quantity of miR-126 mRNA was 2.865 (1.491-4.879)..1.339 (0.904～2.099)、0.310 (0.209～0.858) in normal, benign, and malignant groups, respectively(P<0.001).However, the expression quantity of miR-126 mRNA in normal and benign group has no significant comparisons(P>0.05), those in normal and malignant group, those in benign and maligant group has significant comparisons (P<0.05).2. EGFL7-positive protein was stained in the cytoplasm. The expression of EGFL7 not only located in vascular endothelial cell,but also detected in tumor cell. The rate of EGFL7-positive protein expression was 23.81%(5/21)、52.17%(12/23)、 93.33%(42/45) in normal, benign, and malignant groups, respectively(P<0.001). However, the rate of EGFL7-positive protein expression in normal and benign group has no significant comparisons(P>0.0167), those in normal and malignant group, those in benign and maligant group has significant comparisons (P<0.0167).3. CD34-positive protein represent the detection of MVD in epithelial ovarian tissues. The average MVD was 6.133±2.090、11.478±2.337、21.893±3.223 in normal, benign, and malignant groups, respectively(P<0.001).Any pairwise comparisons were significant variation(P<0.0167).4. The expressions of miR-126 mRNA,EGFL7 mRNA and MVD in EOC was related to FIGO stage and lymph node metastasis(P<0.05);but not related to pathological type and histological differentiation (P>0.05).5. There was negative correlation between miR-126 mRNA and EGFL7 mRNA expression in EOC (r1=-0.413;P=0.005);there was positive correlation between EGFL7 mRNA and MVD expression in EOC (r2=0.362, P=0.015);There was negative correlation between miR-126 mRNA and MVD expression in EOC (r3=-0.909, P<0.001)Conclusions1. miR-126 was under-expressed in the tissue of EOC, suggesting that miR-126 may involved in the process of occurrence and development of EOC.2. EGFL7 and MVD was over-expressed in the tissue of EOC, suggesting that they may involved in the process of occurrence and development of EOC.3. The mRNA expression of miR-126 and EGFL7 in EOC was negative correlation, the expression of EGFL7 mRNA and MVD in EOC was positive correlation,the expression of miR-126 mRNA and MVD in EOC was negative correlation,suggesting that those three factors may be in coordinated with each other in carcinogenesis and progression of EOC. |
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