The Study On Relationship Between Matrix Metalloproteinases And Tissue Inhibitors And Invasion And Metastasis In Ovarian Carcinoma

Ovarian cancer is one of the most common malignant tumors in women.The majority of ovarian cancers are diagnosed in their advanced stage and the relative 5-year survival rate is low.Invasion and metastasis is one of most important characters of ovarian cancer and one of most important factors causing the death of ovarian cancer sufferers.Matrix metalloproteinase-9 (MMP-9)is known to play an important role in cancer cell invasion by mediating the degradation of extracellular matrix.Tissue inhibitors of metalloproteinase-1(TIMP-1)as a natural inhibitor of MMP-9 can regulate MMP-9's activity by bonding with it.In this study, we sought to explore the relationship between MMP-9 and TIMP-1 with clinic-pathologic pattern in ovarian cancer and also to explore the role of MMP-9 and TIMP-1 in invasion and metastatic of ovarian cancer.Elevated Serum Level of MMP-9 in Malignant Ovarian Tumor and Its Clinical SignificanceObjective:To study the relationship between the serum levels of matrix metalloproteinase-9 (MMP-9)in patients with malignant ovarian tumors.Methods:Serum levels of MMP-9 in 55 patients with malignant ovarian tumors,15 patients with benign ovarian tumors and 15 healthy controls were measured by ELISA.Results:The serum levels of MMP-9 in patients with malignant ovarian tumors 472.95±169.48ng/ml were significantly higher than those in patients with benign ovarian tumor 230.99±91.81ng/ml and healthy group 72.99±2.57ng/ml(P＜0.05).The serum levels of MMP-9 in patients after malignant tumor resection 424.11±175.66ng/ml and patients of post-operative recurrent ovarian cancer 478.13±183.90ng/ml were also higher than those in patients with benign ovarian tumor and healthy group(P＜0.05).The serum levels of MMP-9 in pretherapy patients 513.82±133.18ng/ml were higher than those in post-operative patients 437.15±144.41ng/ml in the matched-pairs group(P＜0.05). Conclusions:The serum levels of MMP-9 in patients with malignant ovarian tumors are significantly elevated,which might be used to forecast the malignant change of ovaries,the response to operation of patients with malignant ovarian tumors and the recurrence of the malignant ovarian tumors.Correlation of mutation of TIMP-1 Gene to Clinicopathologic Features of Ovarian CarcinomaObjective:To discuss the correlation of mutation of TIMP-1 gene to clinicopathologic features of ovarian carcinoma and evaluate its role in the occurrence and progression of ovarian carcinoma.Methods:To detect mutation of TIMP-1 gene in 39 patients with malignant ovarian tumors, 10 patients with benign ovarian tumors and 18 healthy controls by polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP).Results:No mutation was detected in the Coding Exon 1-3 and their nearby regions of TIMP-lgene.By detecting the Coding Exon 4 and its nearby regions of TIMP-1 gene in 67 ovaries,we found 1 missense mutation and 1 intron mutation.And 48 examples(17 mutation homozygote,31 mutation)were found to have one SNP site(TIMP-1 3296bp)which SNPsID is rs4898 in the NCBI.Both of the frequencies of the T allele and C allele in this SNP site was 50%.And there were statistical significance between this SNP site and clinical stages (P＜0.05).By detecting the Coding Exon 5 and its nearby regions of TIMP-1 gene in 67 ovaries,we found 2 missense mutation and 1 non-coding exon mutation.We also found 29 examples(6 mutation homozygote,23 mutation heterozygote)having one SNP site(TIMP-1 4251bp)which SNPsID is rs11551797 in the NCBI.The frequencies of the C allele and T allele in this SNP site were seperatively 72.7%and 27.3%.Conclusions:The organization of the malignant ovarian tumor can detect missense mutant, but the organization of normal ovaries and the organization of benign ovarian tumor can't.Missense mutant probably affects the function of TIMP-1 in the organization of the malignant ovarian tumor and the SNP of Coding Exon 4 may be the early event of the generation and development of the malignant ovarian tumor. Correlation of Methylation of TIMP-1 Gene Promoter Region to Clinicopathologic Features of Ovarian CarcinomaObjective:To investigate the correlation between methylation of TIMP-1 genes promoter region and the genesis,the development of ovarian carcinoma.Method:To study methylation of TIMP-1 gene promoter region by detecting 39 patients with malignant ovarian tumors,10 patients with benign ovarian tumors and 18 healthy controls with methylation-specific PCR(MS-PCR).Result:The study showed that the level of methylation of the TIMP-1 gene promoter region CpG island was 83.33%(10/12)in the organization of normal ovaries,100%(10/10)in both the organization of benign ovarian tumors(5/5)and the organization of malignant ovarian tumors(10/10),and the total methylation rate was up to 92.6%.Conclusion:The method of MSP can't distinguish the methylation of TIMP-1 gene promoter region in Xi chromosome of normal female and the methylation of TIMP-1 gene promoter region of the other X chromosome(Xa chromosome)that induces the decreasing of the gene expression of the tumor cell TIMP-1.