The Study On Relationship And Diagnosis Model Between Matrix Metalloproteinase (MMPS), Cathepsin Land Heparanase In Ovarian Cancer

Mortality of ovarian cancer is the highest in gynecological malignancies. Despite the platinum-based chemotherapy and cytoreductive surgery has played a positive role in ovarian cancer management,70% of patients still displays at advanced stage in first diagnosis with newly method due to lacking of effective early diagnosis. The relapse and resistance after surgery and chemotherapy cause the 5-year survival rate has still remained about 30%. Matrix metalloproteinases is known to play an important role in cancer cell invasion by mediating the degradation of extracellular matrix (ECM). In this study, firstly, we sought to explore the relationship between MMP-9, Hpa, CL expressions and clinic-pathologic pattern in ovarian cancer. Secondly, It is also to explore the role of MMP-9, Hpa,CL in invasion and metastatic of ovarian cancer. Thirdly, we also construct and validate an ovarian cancer metastasis diagnosis model which is comprehensive judged by MMP-9, Hpa and CL. Finally, we have made a META analysis of the stroma enzymes expression of relevant researches which have been published in the tissue, and analysis the issues in dispute with evidence-based medicine method.The Detection of MMP-9, Hpa and CL on Tumor Invasion and Metastasis and Its Clinical SignificanceObjective:To explore the matrix enzyme on peripheral blood expression and its relationship with the clinic and pathological characteristics in ovarian carcinomas.Methods:Serum levels of CA125, MMP-9,Hpa and CL in patients with 217 cases of ovarian cancers, 101cases of benign tumors and 101 healthy women as controls were determined by enzyme linked immunosorbent assay(ELISA). Statistical method was used to analyze the clinical and pathological characterization by the analysis of the result.Results:The serum levels of stroma enzymes in ovarian cancers was significantly higher than that in the benign tumors and the control group(p<0.05); The serum expression of stroma enzymes was not associated with pathology types, but associated with pathological types, clinical stage and degree of differentiation. The expression of CL, MMP-9 is associated with peritoneal metastasis. The expression of Hpa is associated with distant metastasis. Correlation analysis showed the relationship between the serum levels of the CL and CA125 is 0.051 and P=0.434, P>0.05, no significant correlation between these two stroma enzymes. Correlation analysis showed the relationship between the serum levels of the Hpa and CA125 is direct correlation, and r=0.183, P=0.005. Correlation analysis showed the relationship between the serum levels of the MMP-9 and CA125 is direct correlation, and r=0.131, P=0.044.Conclusion:The results showed that serum expression levels of These stroma enzymes was correlated with carcinogenesis and progress of ovarian cancer and was expected to become as indicators for judging invasion and metastasis.The Establish and Validation of the combined Mathematical Diagnosis Model of serum levels of Stroma enzymes of Ovarian CancerObjective:To establish the combined diagnosis model of serum levels of stroma enzymes of ovarian cancer and validate the model's effectiveness.Methods:The statistical analysis method (SAS 8.0 software) is used to analyze the mathematical model. The establish method of the diagnosis model is logistic Regresion by using 250 matrix enzyme cases.168 cases was used to validate the model's effectiveness. The comparison result was made between the new model and CA125.Results:The established mathematical diagnosis model is: Logit(P)=14.90-43.24xCL-33.12xhl-43.80xml+71.08x(CLxhl)+55.83x(CLxml)1. Model to judge the nature of the sensitivity of the tumor is 86.4%, specificity is 82.1%, ROC area under the curve is 0.935, P= 0.000. Sensitivity and specificity are higher than any other markers which were detected, so this model is used to determine ovarian cancer are significant.2. Model to judge tumor invasion and metastasis's sensitivity is 70.4%, specificity is 63.9%, ROC area under the curve is 0.732, P= 0.000, sensitivity and specificity are high, so this model is used to judge the invasion and metastasis of ovarian cancer is significant.Conclusion:The model in this study has good diagnostic performance. The sensitivity and specificity of progressing in determining the nature and extent of tumor are high. In this study, many of serum samples collected as much as possible, but the sample size is limited. If a more substantial increase in sample size, debuging and improving the model so that it closer to the actual tumor evolution. It is expected to become as indicators for judging invasion and metastasis.Clinical Value of Liquid Biochip in detection MMP-9, Hpa and CL's value of serumObjective:To explore the matrix enzyme on peripheral blood liquid biochip expression and its relationship with the clinic and pathological characteristics in ovarian carcinomas.Methods:Serum levels of CA125, MMP-9,Hpa and CL in patients with 96 cases of ovarian cancers,79cases of benign tumors and 55 healthy women as controls were determined by flow fluorescence assay. Statistical method was used to analyze the clinical and pathological characterization by the analysis of the result.Results:1. Patients with malignant ovarian tumor expression levels of matrix enzymes were significantly higher than benign group and control group, the difference is significant (P<0.05); in serum of patients with malignant ovarian tumors, the expression of matrix enzymes and pathological types has no relationship.2. liquid silicon substrate enzyme assay for determining the quality of judging the sensitivity of ovarian cancer are:CL 84.3%, Hpa 72.3%, MMP-973.5%; specificity, respectively:CL 76.0%, Hpa 84.0%, MMP-988.0%.3. Liquid silicon substrate enzyme assay for the judgement to judge the sensitivity of ovarian tumor metastasis are:CL 867.9%, Hpa 62.5%, MMP-975.0%; specificity, respectively:CL 66.7%, Hpa 63.0%, MMP-963.0%.4. Detection of liquid silicon substrate enzyme levels to determine the nature of the test performance of ovarian cancer is generally better than ELISA, especially in benign and malignant tumors when judging the specificity was significantly higher than ELISA.5. Liquid chip technology and the ELISA assay test ovarian cancer metastasis have almost the same performance.Conclusions:Liquid Biochip can be used to detect multi tumor marker, and can increase the diagnosis sensitivity.The Meta Analysis of Relationship Between Several Stroma enzymes and Invasion and Metastasis in Ovarian CancerObjective:To explore the relationship of the value of stroma enzymes in ovarian and the ovarian cancer.Methods:We have searched CBMdisc database, EMBASE database and MEDLINE database, and found 16 papers between January 2005 and December 2009 complied with the standard. The survival results have been obtained through the study of the heterogeneity and fixed effects and random effects models. Statistical methods have been used by utilizing RevMan 4.2.10 software.Results:1. MMP-9 expression in the study, included 7 studies, OR= 11.43, Or 95CI is 6.78,19.27, P <0.00001. Matrix metalloproteinases in malignant and non-malignant ovarian tumor tissues and contents are significantly different; studies are homogeneous.2. Hpa expression in the study, included 6 studies, OR= 8.62, Or 95%CI is 4.57,15.28, P <0.00001. Heparanase in malignant and non-malignant ovarian tumor tissues and contents are significantly different; study are homogeneous.3. CL expression in the study, included 3 studies, OR= 2.70, Or 95CI is 0.26,27.97, P=0.41. Cathepsin in malignant and non-malignant ovarian tumor tissues and contents are significantly different; study are heterogeneity.Conclusions:The Meta analysis result has showed that the expression of stroma enzymes in much higher in ovarian cancer than that in normal ovarian tissue. Because the evidence-based medicine method has only several distribute examples, the effect of the expression of stroma enzymes in ovarian cancer is not very convincing. It needs more examples to research and study. Anyway, stroma enzymes have the possibility to be the new maker of ovarian cancer.