| BackgroundOvarian cancer is very common in gynecological malignancies. The mortality of ovarian cancer is far more than the mortality of cervical cancer and endometrial cancer. Ovary is in the bottom of pelvic cavity. Because of a lack of specificity of clinical symptoms, more than2/3belong to the late stage when definites diagnosis. The five-year survival rate of early epithelial ovarian cancer (I and II stage) is up to70%-90%, while the five-year survival rate is only20%of the late stage (III and IV stage). Therefore, looking for the sensitive indicators of dignosis and detection of the ovarian cancer, and the biological indicators of the valuable guide to prognosis and clinical treatment of ovarian cancer has bacome the hot point of the research of the ovarian tumor.HGF/c-Met signaling pathway play an important role in cell growth, angiogenesis, the process of epithelial mesenchymal and the proliferation, invade transfer of the cell. Its abnormal activation can lead to the formation and the metastasis of a variety of malignancies such as ovarian cancer, lung cancer, breast cancer and the liver cancer, especially related to the invade and transfer of the malignancies.C-Met is a former cancer gene, belongs to the kind of tyrosine activity of growth factor receptor. C-Met code the protein of cytoplasm which is the receptor of the hepatocyte growth factor. It has tyrosine kinase activity, and involves in signal transduction, regulation, cytoskeleton reconstruction, and plays an important role in the process of cell proliferation, differentiation and restore. At present, some research suggests that the occurrence and development of many human tumors is very closely of the differentially expression and abnormal structure of c-Met.Metastasis associated in colon cancer-1is a new gene associated with colon cancer metastasis, discovered by Stein etal in2009. MACC1is the very important regulatory factor of the HGF/c-Met signaling pathway that can increase the level of the transcription expression of the HGF receptor c-Met, thus promoting the proliferation, invasion and metastasis of the cells. MACC1can activate the expression of c-Met, leading to the overreaction of HGF, and HGF can lead MACC1transfer from the cytoplasm to the nucleus. MACC1can combine with Sp-1sector of promoter, and can further activate the transcription of c-Met in the nucleus. Thus, MACC1involved in HGF/c-Met signaling pathway, forming an unusual positive feedback loop.Currently, the research of MACC1is still in start-up period at home and abroad, the related research is still relatively few, especially in the aspect of gynecologic tumors. However, as a newly discovered gene, which promote the formation and metastasis of cancer has attracted much attention, the related studies are gradually underway. The experimental studies of the transcription target c-Met of MACCl have shown that in the known tumors of high c-Met expression, the expression of MACC1is higher. The consistency of the high expression of c-Met in experiments and MACC1in forecasts prompt that, MACC1not only in colon cancer, but also in other malignancies play an important roles. As the highest mortality of women malignancy, but still lack early diagnosis and prognostic indicators of ovarian cancer. The research has been shown that c-Met is high expression in ovarian cancer, at the same time, HGF and c-Met as the factors of HGF/c-Met signaling pathway, are both high expression in ovarian cancer, and the overexpression is closely related to the formation and progression of the ovarian cancer. ESTProfileViewer and VirtualNorthern database have show that MACC1has higher expression in both normal ovary tissue and ovarian cancer.We study of the expression of MACC1in52patients with epithelial ovarian cancer,19patients with benign epithelial tumor and20normal ovaries by RT-PCR, and detected the expression of MACC1protein and c-Met protein in52patients with epithelial ovarian cancer,19patients with ovarian benign epithelial tumor and20normal ovaries by immunohistochemistry methods. And the correlation between the expression of MACC1and c-Met protein with tumor clinical stages, histopathology type was analyzed, and analyze the dependability of MACC1and c-Met in ovarian epithelial cancer. We further explore the relation between MACC1/c-Met and the formation development of epithelial ovarian cancer, and reveal the molecular biological mechanism of the ovarian epithelial cancer.ObjectiveTo detect the difference expression of MACC1mRNA and protein, c-Met protein in different ovarian tissues, and to analyze the relation between the expression of MACC1and c-Met with the clinicopathologic factors of epithelial ovarian cancer. To explore the role of MACC1and c-Met in the development of the epithelial ovarian cancer. To reveal the mechanisms of the occurrence and development of epithelial ovarian cancer, and provide new ideas to guide the clinical diagnosis.Method1Revers-transcription PCR was used to detect the MACC1mRNA expression in52patients with epithelial ovarian cancer,19patients with benign ovarian tumors and20normal ovaries, and analyze the difference of the three tissues.2Immunohistochemistry was used to detect the protein expression of MACC1and c-Met in52patients with epithelial ovarian cancer,19patients with benign ovarian tumors and20normal ovaries, and analyze the difference of the three tissues. And further explore the relation between the expression of MACC1/c-Met with the clinical and pathological factors of epithelial ovarian cancer. And analyze the relationship between the protein expression of MACC1and c-Met. 3Statistical analysis:the SPSS statistical package program17.0for all analysis. The level of expression among different tissues were tested by One-way analysis of variance (by the normality test and homogeneity of variance test). The LSD test was used in two groups. The enumeration data was analyzed by chi-square test and correction chi-square test. The correlation analysis was analyzed by pearson correlation test. Significant level is a=0.05.Result1. The relative expression level of MACC1mRNA in normal ovary is0.177±0.056, in benign epithelial ovarian tumors is0.247±0.064, and in epithelial ovarian cancer is0.838±0.061. The relative expression of the ovarian cancer is higher than in the normal ovary and benign epithelial ovarian tumors (F=404.0, P=0.000), but the difference between benign epithelial ovarian tumor tissue and normal tissue is not statistically significant (P=0.104>0.05).2. The positive rate of MACC1protein expression in normal ovarian, benign epithelial ovarian tumor and epithelial ovarian cancer were5.0%(1/20),15.8%(3/19) and73.1%(38/52) respectively. The relative expression of the epithelial ovarian cancer is higher than in the normal ovary and benign epithelial ovarian tumors (X2=28.893, P=0.000<0.05), but the difference between benign epithelial ovarian tumor tissue and normal tissue is not statistically significant (P=0.560>0.05).3. The positive rate of c-Met protein expression in normal ovarian, benign epithelial ovarian tumor and epithelial ovarian cancer were10.0%(2/20),21.1%(4/19) and78.8%(41/52) respectively. The relative expression of the ovarian cancer is higher than in the normal ovary and benign epithelial ovarian tumors (χ2=36.417, P=0.000<0.05), but the difference between benign epithelial ovarian tumor tissue and normal tissue is not statistically significant (P=0.608>0.05).4. The overexpression of MACC1protein in epithelial ovarian cancer was significantly associated with clinical FIGO stage, histological type and lymphatic metastasis, but not associated with ages, histological and ascites formation. The positive expression of MACC1protein in early ovarian cancer (I and II stage) was lower than advanced ovarian cancer (III and IV stage)(P=0.000), and its expression in poorly differentiated ovarian cancer (G2and G3) was significantly higher than that in G1stage (P=0.026<0.05). The positive rate expression of MACC1in absence of lymph node metastasis and lymph node metastasis was63.6%(21/33) and89.5%(17/19), respectively. The difference between the two groups was statistically significant (P=0.038<0.05).5. The upregulation of c-Met protein in epithelial ovarian cancer was releated with clinical stage(χ2=9.167, P=0.002), histological type(χ2=4.221, P=0.040) and lymphatic metastasis (χ2=4.995, P=0.025), The higher expression of c-Met in the advanced ovarian cancer, the poorly differentiated ovarian cancer and with the lymph node metastasis. And the expression of c-Met protein was not associated with ages, histological and ascites formation.6. The expression of MACC1protein was positive correlated with the c-Met protein in epithelial ovarian cancers (p=0.020<0.05, r=0.385).Conclusion1. The expression of MACC1mRNA and protein, c-Met protein in epithelial ovarian cancer was higher than its in normal tissues and benign ovarian tumors. It may involved in the malignant transformation of epithelial ovarian tumors.2. In epithelial ovarian cancer, upregulation of MACC1and c-Met protein was releated with advanced FIGO stage, poor differentiation and lymphatic metastasis. It prompt that MACC1and c-Met may involved in the development of the ovarian cancer, MACC1and c-Met may be considered as a new marker for the diagnosis and prognosis of ovarian cancer.3. The expression of MACC1protein was positive correlated with the c-Met protein in epithelial ovarian cancers. To detect the protein of MACC1and c-Met may be helpful in prognosis and maligant degree. |
PDF Full Text Request