| Ovarian epithelial cancer as one of common malignant tumor of female reproductive system, Gynecologic malignant tumor mortality in first place. No obvious symptoms, early onset of the disease is more hidden, lack of effective early diagnostic method at the same time, tend to have occurred when confirmed. Current overall 5 years survival rate is still hovering at about 30% ~ 40%, the overall outcome is not satisfied.Therefore, to explore with the invasion and metastasis of ovarian cancer occurrence, development and related factors is particularly important.Micro RNAs are a class of the total length of about 22 nt noncoding small single-stranded RNA molecules. At present a large number of studies have shown that abnormal expression of micrornas are closely associated with the occurrence and development of various diseases. Many micrornas proved has played a key role in regulating cell growth, differentiation, In recent years, the study found that micrornas are also involved in some occurrence, development and metastasis of the tumor and the effect is similar to or cancer suppressor genes. Numerous studies have found that mi R-181 a is closely related to the occurrence of a wide variety of tumor development, such as gastric cancer,breast cancer, cervical cancer, but in ovarian cancer research reports.TGF-β is a kind of structure and function closely related to the activity of peptide family. At present, the research has confirmed that TGF-β signaling pathways play an important role in a variety of malignant tumors. A lot of research has shown that TGF-β signaling pathways in different development period of the malignant tumors differ in the opposite effect. Early in tumorigenesis,give priority to with inhibiting effect.its main expression in promoting cell differentiation and apoptosis. promote the white blood cell aggregation, inhibit tumor inflammation, and to inhibit the action of the source of stromal cells division element, But, in the progress, tumor stage, TGF-β lose monitoring of tumor inhibition,promote the development of tumor. This mainly displays in:(1) it can promote tumor escape immune surveillance mechanism, promoting tumor growth factor;(2) the tumor invasive enhancement. such as led to qualitative between epithelium. promote tumor metastases formation;(3) promote the invasion and metastasis of tumor and metastatic tumor clone growth.TGF-β1 is a kind of cell proliferation inhibitor,more widely involved in cell differentiation,proliferation,morphology change, adhesion, transfer, extracellular matrix and apoptosis,are the main members of the family of TGF-β. Reports of TGF-β1 as target genes of mi R-181 a, TGF-β1 expression in liver cancer induced by mi R-181 a. TGF-β R1 as TGF-β, one of the most important receptors, another member of the family of TGF-β, lack of TGF-β R1 mutant cells of TGF-β1.Zhong found that TGF-β1 expression in pancreatic cancer tissue, TGF-β R1 is reduced,speculated that TGF-β R1 expression is reduced tumor cells of TGF-β1 reactive weakening one of the reasons, its low expression may escape for pancreatic cancer TGF-β one of negative growth control mechanism. Mi R-181 a in epithelial ovarian cancer is available at the moment in the mechanism of action is unclear, less literature reported mi R-181 a and TGF-β a key factor in signaling pathways TGF-β1 and TGF-βR1. This study through the q RT-PCR and immunohistochemical methods in different pathological characteristics of ovarian epithelial tissue mi R-181 a m RNA.TGF-β1 m RNA. TGF-βR1 m RNA and the latter two corresponding protein expression, discusses its in ovarian epithelial tumor occurrence, development and transfer of the role and application value.ObjectiveThis study through the detection of mi R-181 a, TGF-β 1, TGF-β R1 expression in different pathological characteristics of ovarian epithelial tumors, a preliminary analysis of the possible role in epithelial ovarian cancer occur in developing and significance; Through the analysis of m RNA expression of the correlation between the three in the epithelial ovarian sex, explore mi R-181 a in malignant ovarian epithelial tumors of molecular mechanism of the occurrence, development and metastasis.Materials and methods1 The research objectCollected from March 2010 to September 2014 in the third affiliated hospital of zhengzhou university and the first affiliated hospital of zhengzhou university line of surgical treatment of 130 cases of patients with ovarian epithelial tissue, aged 17 ~ 76 years old, the average age of 47.8 years, 130 cases of normal group of 35 cases, 30 cases of benign group, 65 cases of malignant group. Group of normal ovarian tissue from patients with ovarian resection for benign uterine lesions; Benign and malignant groups of ovarian tissue based on preoperative no chemotherapy, radiation therapy, such as the auxiliary treatment of primary epithelial ovarian cancer patients. Malignant group according to the FIGO stage(2000) : Ⅰ, Ⅱ period in 16 cases, Ⅲ, Ⅳ 49 cases; Low differentiation 33 cases, high, 32 cases of differentiation; mucous cystadenocarcinoma 14 cases, Serous cystadenocarcinoma 39 cases, 12 cases of end ometrial carcinoma. With lymph node metastasis, 38 cases with no lymph node metastasis of 27 cases. All cases were confirmed by surgery and pathology.2 The research methodApplication q RT-PCR technique to detect three groups of mi R-181 a m RNA, TGF-β1 m RNA and the expression of TGF-βR1 m RNA situation. Application of immunohistochemistry technique to detect TGF-β1 protein in three groups and TGF-β R1 protein expression.3 The statistical methodsUsing SPSS18.0 software for statistical analysis. Measurement data(?x + s) by using two independent sample t-test and single factor variance analysis, inspection level of α=0.05, inspection level between two groups to compare=α/more= 0.0167. Count data comparison with chi-square test, between two groups to compare the two independent groups of binary classification chi-square test, inspection level of α=0.05, between two groups to compare inspection level α=α/more= 0.0167.Correlation analysis using Pearson correlation analysis,inspection level of α= 0.05.Results1. The relative expression quantity of the mi R-181 a m RNA in the normal group, benign and malignant group were 3.343±0.216、3.217±0.354、7.348±0.931 in the three groups of mi R-181 a m RNA expression difference was statistically significant(P< 0.05). Two in three groups: mi R-181 a m RNA expression of malignant group was obviously higher than that of benign group and normal group, the difference was statistically significant(P<0.0167); Benign group there was no statistically significant difference compared with normal group(P> 0.0167).2. The relative expression quantity of the TGF-β1 m RNA in the normal group,benign and malignant group were 1.132±0.404、1.237±0.091、3.154±0.231 in the three groups of TGF-β1 m RNA expression difference was statistically significant(P <0.05). Two in three groups: TGF-β1 m RNA expression of malignant group was obviously higher than that of benign group and normal group,the difference was statistically significant(P<0.0167); Benign group there was no statistically significant difference compared with normal group(P>0.0167).3. The TGF-β R1 m RNA in the normal group, the relative expression of benign and malignant group were 5.012± 0.935、4.947±0.786、1.107±0.115 in the three groups of TGF-β R1 m RNA expression difference was statistically significant(P< 0.05). Two in three groups: the expression of TGF-βR1 m RNA malignant group was obviously lower than that of benign group and normal group, the difference was statistically significant(P<0.0167); Benign group there was no statistically significant difference compared with normal group(P>0.0167).4. TGF-βl protein positive expression in cell plasma, criterion with orange-brown staining positive cell cytoplasm. See figure 1. TGF-β1 protein in the normal group, the positive expression rate in benign and malignant group were 37.1%(13/35), 20.0%(6/30), 69.2%(45/65), compare the difference was statistically significant between the three groups(χ2= 22.704, P< 0.05). Comparing two: malignant group of TGF-β1 protein positive expression rate is higher than in normal group and benign group, differences were statistically significant(P<0.0167); Benign group there was no statistically significant difference compared with normal group(P>0.0167).5.TGF-βRl protein positive expression in cytoplasm, criterion with orange-brown staining positive cell cytoplasm. See attached figure 2. TGF-βR1 protein in normal group, the positive expression rate in benign and malignant group were 60%(21/35), 73.3%(22/30), 43.1%(28/65), compare the difference was statistically significant between the three groups(χ2= 8.141, P<0.05). Pairwise comparison: malignant group of TGF-βR1 protein positive expression rate is lower than the benign group and normal group, the differences were statistically significant(P<0.0167); Benign group there was no statistically significant difference compared with normal group(P>0.0167).6. In epithelial ovarian cancer tissues, mi R-181 a m RNA, TGF-β1 m RNA and TGF-βR1 m RNA and protein in both the expression and its pathological type, age has nothing to do all(P>0.05), and is associated with clinical stage, histological grade, lymph node metastasis(P<0.05). In the higher FIGO staging, histological grade is lower, with lymph node metastasis of epithelial ovarian cancer tissues, mi R-181 a m RNA, TGF-β1 m RNA and TGF-β1 protein the higher the expression rate, TGF-β R1 m RNA and protein expression rate is lower;In three different pathological type of comparison, mi R-181 a m RNA, TGF-β1 m RNA and TGF-βR1 m RNA and protein expression differences between the last two no statistical significance(P>0.05).7. Mi R-181 a m RNA, TGF-β1 m RNA and TGF-βR1 m RNA expression in ovarian epithelial cancer by Pearson correlation analysis showed that the consistency of analysis in malignant ovarian epithelial tumor tissues, mi R-181 a m RNA and TGF-β1 m RNA expression levels were positively correlated(r = 0.810,P < 0.05), and negatively correlated with TGF-βR1m RNA(r = 0.769,P < 0.05); TGF-β1 m RNA and TGF-β R1 m RNA showed a negative correlation(r = 0.837, P < 0.05).Conclusions1. In epithelial ovarian cancer, mi R-181 a and TGF-β1 high expression of TGF- β R1 lower expression, three may be involved in the occurrence and development of ovarian epithelial sex.2. Mi R-181 a high expression of epithelial ovarian cancer tissues TGF-β1 high expression, both has significant positive correlation, mi R-181 a, TGF-β1 high expression of epithelial ovarian cancer tissues TGF-βR1 lower expression, both has significant negative correlation. In epithelial ovarian cancer, mi R-181 a may be a mechanism induced the expression of TGF-β1, inhibit the expression of TGF-βR1.3. Mi R-181 a and TGF-β1 high expression of TGF-βR1 lower expression suggests patients prognosis is poor, the three possible synergies involved in epithelial ovarian cancer invasion and metastasis. |
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