Study Of Expression And Correlation Of Matrix Metalloproteinase-26, -9 And TIMP-4 In Cervical Cancer

Background:Cervical cancer is the second largest cancer affecting women's health in the world, although the new method of examination and treatment appear unceasingly, but many patients have transferred due to the lack of specific indicators for the early diagnosis.Tumor metastasis is still the root causes of deaths. Therefore it has been the key topic that the study about transfer mechanism. Matrix metalloproteinases play an important role in the tumor transfer, because which has the formidable function of degeneration extracellular matrix, that is, degenerate BM and ECM and enhance tumor blood vessel to produce, promote tumor cell to attack and the shift.As was known, one of the conditions of the transfer for tumor cells is that through the first histological barriers, which is composed of the basement membrane and extracellular matrix and limit tumor cells to transfer, and the main component of the barrier is collagenⅣ.MMP-9 is a closely related member with tumor transfer in the family of MMPs due to its powerful function in degrade typeⅣcollagen, so MMP-9 participate in the transfer process of a variety of tumors and it has been a research focus, but related research about MMP-9 are few in cervical cancer, and moreover the view of people is also inconsistent .MMP-26 is more unique in structure and function in the MMPs family.So it has been a research hotspot after the discovery. The research from domestic and foreign confirmed that MMP-26 play an important role in regulating normal menstrual cycle and occurrence and development of endometrium cancer, but it was still blank about cervical cancer research in domestic and foreign. TIMP-4, recently discovered and new number of TIMPs family, which are different from TIMP-1, 2 and 3 in the expression and regulation mechanism, and can inhibit a variety of MMPs, at the same time, TIMP-4 was considered that it is the physiological inhibitor of MMP-26, and the research was still blank about the relationship between TIMP-4 and cervical cancer in domestic and foreign.The purpose of this article is that detect the expression of MMP-26, MMP-9 and TIMP-4 in cervical carcinoma. Furthermore we sought to determine any correlation between the expression of MMP-26, MMP-9 and TIMP-4 with different pathological features and also tried to find any correlation among them three. The goal of this research is that identify the role about MMP-26,MMP-9 and TIMP-4 in the occurred and developed process of cervical cancer and further study the relationship among the three, it lays the foundation on the study between members of MMPs and TIMPs and incidence and transfer mechanism of cervical cancer for next step.Methods:1. Immunohistochemistry to detect the expression of MMP-26, MMP-9 and TIMP-4 in normal cervical tissue, cervical carcinoma in situ and invasive carcinoma of cervix. Furthermore, we sought to determine any correlation between the expression of MMP-26, MMP-9 and TIMP4 with different pathological features and also tried to find any correlation among three.2. RT-PCR method to detect the expression MMP-26, MMP-9 and TIMP-4 in fresh frozen normal cervical tissues (n = 3), cervical carcinoma in situ (n = 3), invasive carcinoma of cervix (n=32).furthermore, we sought to determine any correlation between the expression of MMP-26, MMP-9 and TIMP-4 with different pathological features.3. All experimental data were analyzed by SPSS16.0statistical software. According to different comparison,χ2 test, rank sum test and Spearman correlation analysis were used, P <0.05 was considered statistically significant.Results:1. Respectively, the positive expression rate of MMP-26 is 10.00%,83.33%和82.47% in the normal cervix, carcinoma in situ and invasive carcinoma of cervix. Statistical results showed, compared with normal cervix, that the expression of MMP-26 increased in carcinoma in situ and invasive carcinoma of cervix (P <0.05). The expression of MMP-26 is closely related with the depth of myometrial invasion and lymph node metastasis, but it is not closely related with the histological type, clinical stage, grade and patient age.The expression of MMP-26 have enhanced trend with the depth of myometrial invasion and the expression in carcinoma with lymph node metastasis is significantly higher than that without lymph node metastasis.2. Respectively, the positive expression rate of MMP-9 is 10.00%,50.00%和70.10% in the normal cervix, carcinoma in situ and invasive carcinoma of cervix. Statistical results showed, compared with normal cervix, that the expression of MMP-9 increased in invasive carcinoma of cervix (P <0.05). The expression of MMP-9 is closely related with the grade of cervical cancer and patient age. Compared with well-differentiated and moderately differentiated cervical cancer and young, the expression of MMP-9 is enhanced the patients with poorly differentiated and aging; But it is not closely related with the histological type, clinical stage, the depth of myometrial invasion and lymph node metastasis.3. Respectively, the positive expression rate of TIMP-4 is 100.00%,83.33%和74.23% in the normal cervix, carcinoma in situ and invasive carcinoma of cervix. Comparison among the three was no significant difference (P> 0.05).The expression of TIMP-4 is closely related with clinical stage of cervical cancer. compared with cancer in PhaseⅡ, it is higher than cancer inⅠPhase. But it is not closely related with the histological type, pathological grade, depth of myometrial invasion, lymph node metastasis and patient age.4. In the cervical carcinoma, the expression of TIMP-4 protein and MMP-26 protein, and TIMP-4 protein and MMP-9 protein respectively were negatively correlated (P <0.05), correlation coefficient is 0.259 and 0.327. MMP-26 protein and MMP-9 protein expression had no obvious correlation (P> 0.05). 5. RT-PCR results showed that, the positive expression rate of MMP-26, MMP-9 and TIMP-4mRNA respectively is 87.50% 84.38% and 90.63% in cervical cancer. The expression of MMP-26mRNA is not closely related with the pathological grade of cervical cancer. MMP-9 mRNA and TIMP-4mRNA expression is closely related to pathological grade. The positive expression rate of MMP-9 has been an upward trend, with an increased pathological grade, the expression of TIMP-4 in the poorly and moderately differentiated cancer is higher than which of well-differentiated cancer.Conclusion:1. Compared with carcinoma in situ and invasive carcinoma of cervix, the expression of MMP-26 is low in normal cervix. its expression is closely related with the depth of myometrial invasion and lymph node metastasis, but is not closely related with the histological type, clinical stage, pathological grade and age. It suggests that MMP-26 may play an important role in the process of occurrence, early infiltration and distant metastasis of cervical cancer.2. Compared with invasive carcinoma of cervix, the expression of MMP-9 protein is low in normal cervix and is closely related with the grade of cervical cancer and patient age. But it is not closely related with the histological type, clinical stage, the depth of myometrial invasion and lymph node metastasis.3. Compared with the normal cervix, the expression of TIMP-4 has been a downward trend in the cervical carcinoma in situ and invasive carcinoma of cervix. The expression of TIMP-4 is closely related with clinical stage of cervical cancer. But it is not closely related with the histological type, pathological grade, depth of myometrial invasion, lymph node metastasis and patient age.4. In the cervical carcinoma, the expression of TIMP-4 protein and MMP-26 protein, and TIMP-4 protein and MMP-9 protein respectively were negatively correlated. MMP-26 protein and MMP-9 protein expression had no obvious correlation.