Study Of Effection And Correlation Of Metastasis Suppressor Gene Kail/CD82,ME491/CD63 And Integrinα5 Gene In The Invasion And Metastases Of Ovarian Cancer

Xia zhijun Zhang shulanObjective: To explore the effection of metastasis suppressor gene Kail/CD82, ME491/CD63 and integrin α 5 gene and their compounds in the invasion and metastases of ovarian cancer, and the clinical significance of Kail/CD82 and ME491/CD63 gene diagnosis. The invasion and metastases are an important character of malignant tumor and also are the main cause of dead for ovarian cancer. While diagnosis and treatment method of ovarian cancer is unceasing amelioration therapeutic efficacy is not satisfactory. At preasent, 5 year's survival rate of ovarian cancer is to wonder between 30% and 40%. The basic reason existed is that modern medicine be impossible to control and block the invasion and metastases. Because the position and biology particularity of ovarian's anatomy, cancer cell had existenced and metastasis when 70% patien final diagnosis were done. Clinical statistics show that above 80% patien dead for invasion and metastases, such study ovarian cancer invasion and metastases is extremely important thing. Thus, thatinvestigation had became the hot spot study item in tumor domain. At present, we had found anti-metastasis gene for about 10 or so. Their capital function are anti-metastasis. Now inhibition gene main are: MHC , nm23, Kail/CD82> KISS, MKK4, BrMSK E-Cadherin> DCC\ TIMP-K TIMP-2> SeeCK, gelsolin> CD9> CD63> CSK, WDNM-1 and WDNM-2. CD82, CD63 and CD9 are a kindred fember and especially noticed.Methods: The expression levels of Kail/CD82> ME491/CD63 and integrins a 5 gene mRNA and proteins were evaluated by using hybridization in site and RT-PCR in normal ovarian tissues, ovarian benign tumor tissues, ovarian borderline tumor tissues and ovarian cancer tissues. Analyze the expression levels of Kail/CD82> ME491/CD63 and integrins a 5 genes and proteins by multivariant analysis statistically. Explore their effects on the invasion and metastases of ovarian cancer . To study the correlation of patien age at surgery, histological differentiation, lymph metastades, TNM grading and pathological typing. Results: The results got from hybridization in site which showed the exact biological effects of Kail/CD82 , ME491/CD63 and integrins a 5 in ovarian cancer tissues were consistant with that got from RT-PCR.(DThe results showed the exact biological effects of Kail/CD82 in ovarian cancer tissues from RT-PCR and HIS. There was no statiatically significant relationship between gene expression and age at surgery orclinical-pathological staging, P>0.05. There was significant difference between Gi-G2and G3 P<0.01, while no difference between Gi and G2, P>0.05. We found obvious low expression levels in IV group(III,IV period) .Significant differences were noted between expression levels in IV groups and in II, III or IV ( I , II period)groups . PO.01; There was no significant differences among expression levels in II, III or IV ( I , II period)groups. There was significant difference between expression levels in tissues with lymph metastases and tissues without lymph metastases, P<0.01.About whether the high expression levels in tissues without lymph metastases can predict that the tumor cells have metastasized to lymph nodes, we need further study.?Expression of CD63 took on cooperativity in level of protein and mRNA, and descent tendency accompany staging reduce and metastas of tumor. The results showed there was no statiatically significant relationship between gene expression and age at surgery or clinical-pathological staging, P >0.05. There was significant difference between GpG2and G3 P<0.01,while no difference between Gj and G2, P>0.05. We found obvious low expression levels in IV group (IUJVstage) .Significant differences were noted between expression levels in IV group and in II, III or IV ( I , II stage)groups . P<0.01; There was no significant differences among expression levels in II, III or IV ( I , II stage)groups. There was significant difference betweenexpression levels in tissues with lymph metastases and tissues without lymph metastases, P<0.01.?Expression of integrins a 5 took on cooperativity in level of protein and mRNA, and descent tendency accompany staging reduce and metastas of tumor. The results showed there was no statiatically significant relationship between gene expression and age at surgery or clinical-pathological staging, P >0.05. There was significant difference between GrG2and G3 ;P<0.01,while no difference between G( and G2, P>0.05. We found obvious low expression levels in IV group (IUJVstage) .Significant differences were noted between expression levels in IV group and in II, III or IV ( I , II stage)groups . PO.01; There was no significant differences among expression levels in II, III or IV ( I , II stage)groups. There was significant difference between expression levels in tissues with lymph metastases and tissues without lymph metastases, P<0.01. Decrease or deletion of expression levels in tissues with lymph metastases will lead to the descent of ability for ovario-epithelial cells inves basement membrane and the diastasis form epithelial lining and easy to break through basement membrane, thus formation interstitial infiltration.All in all, there was no statiatically significant relationship between gene expression and age at surgery or clinical-pathological staging, P>0.05. The reasons maybe were that them had nothing to do withpathologic status or that the sample was mall. What was not consistant with previous reports was that there was significant difference between GrG2and G3 P>0.01,while no difference between G{ and G2,P>0.05.The differences among expression levels corresponding to individual histological grading especially the absence in low grading showed that tumor cells grow, invasive and metastasize under no control when anti-oncogenes are down-regulated.We found obvious low expression levels in high-grade tumors(III,IV grade) .Significant differences were noted between expression levels in high-grade tumors and in benign tumors, borderline tumors or low -grade tumors. P<0.01; There was no significant differences among expression levels in benign tumors, borderline tumors and low -grade tumors. There was significant difference between expression levels in tissues with lymph metastases and tissues without lymph metastases, P<0.01.About whether the high expression levels in tissues without lymph metastases can predict that the tumor cells have metastasized to lymph nodes, we need further study. The positive expression in early stage which is related with early active of oncogenes and incomplete inactive of anti-oncogenes is thought as a kind of compensation. Along with the invasion and metastases of tumors , anti-oncogenes are down-regulated even absent because of complete close. Mashimo el studied the relationship between Kail gene and p53and reached a conclusion that the reduced expression of Kail gene which can lead to invasion and metastases of ovarian cancer is resulted from the absent functions of p53 .The Kail/CD82,ME491/CD63 genes and the compounds with integrins a 5 are maybe the most direct factors for invasion and metastases of ovarian cancer.Conclusions: There are coincidence gene expression tendancy in ovarian cancer. Three genes are accompany the period raised, and their mRNA and protein expression are gradually decrease. There are satisfactory positive express in ovarian benign tumor. The Kail/CD82, ME491/CD63 and integrins a 5 genes are definitely correlated with ovarian cancer. Different expression levels in tissues of primary focus, metastasic focus and lymph nodes show that these genes are invasion and metastases associated genes , maybe the direct genes. Carcinogenesis will occur or invasion and metastases of cancer have already happened when these genes are down-regulated even absent. The changs of three genes is correlation with tumor differentiation degree, not pathologic taying. As a unusual tipe tumor, borderline tumor occurrenced different gene expression and its deletion expression is match its clinical easy metastasis propert. This is helpful for us to predict the prognosis and make treatment projects .Concerning whether they can be considered as independent molecular biological markers to predict the prosnosis of ovarian cancer or indications to screen high-risk patients without metastases to lymph...