| Background and objectiveCervical carcinoma is a frequent gynecologic malignant tumor. Operation and radiotherapy are the main therapy methods. In spite of improvement of operation skill, radiotherapy equipment and technical level, total five year survival rate of cervical carcinoma fluctuates around 50%, without distinct advancement. Metastasis is a major cause impacting on prognosis. At present, more and more studies are focusing on how to increase the therapy effect on limited cervical carcinoma of progressive stage.Infiltration and metastasis are the basic biological characteristic of malignant tumor. Metastasis of tumor is a sequential process of interaction between tumor cells and host cells, which is highly selective with multistep and multifactor. Tumorigenicity is necessary, but gene expression of cells requires further changes for metastasis, such as metastasis suppressor gene and matrix metalloproteinases (MMPs), et al. KiSS-1 is a new metastasis suppressor gene, which restrains metastasis of tumor by suppressing transmigration ability, promoting apoptosis, inhibiting tumor cell proliferation, and down-regulation of expression of matrix metalloproteinases-9(MMP-9). KiSS-1 gene correlates with metastasis of various malignant tumors and indicates prognosis information. MMP-9 is a maximal molecular weight enzyme of MMPs, which correlates with potentials of invasion and metastasis in many malignant tumors. Neither the correlation of KiSS-1 gene and cervical carcinoma, nor the interaction of KiSS-1 and MMP-9 in cervical carcinoma has been reported in and out. We detected the expression of KiSS-1 and MMP-9 in cervical tissue, analyzed relationships among KiSS-1, MMP-9 and squamous cell carcinoma of the cervix (SCC), discussed the interaction between KiSS-1 and MMP-9 in SCC, aiming at supplying diagnosis and prognosis indicator and new therapy target site for SCC.Methods1. To collect normal cervix epithelial tissue of 12 cases, CIN of 14 cases, SCC of 46 cases, to detect expression of KiSS-1 mRNA by ISH, and analyze the association between the expression and clinical pathological factor of SCC, correlation between KiSS-1 mRNA and KiSS-1 protein(metastin) in all above tissues.2. To detect expression of metastin and MMP-9 protein in all above tissues by immunohistochemistry and analyze the association between both expression and clinical pathological factor of SCC, interaction between metastin and MMP-9 protein in SCC.3. Statistical treatment: data were treated by SPSS13.0 statistical software. To compare with rate of sample by Chi-squared test (a correction included) and Fisher's exact probability test. To test correlation between 2 samples by Spearman Correlation. Statistical significant level was considered as "alpha eaquals 0.05"(α=0.05).Results1. The positive rate of KiSS-1 mRNA in normal cervix epithelial tissue, CIN, and SCC was 100% (12/12), 85.7% (12/14) and 32.6%(15/46), respectively. There was statistical significance among there groups(P<0.01). The positive rate of SCC group was significantly less than CIN and normal cervix epithelial tissue group, difference had statistical significance(P<0.01). The difference between CIN and normal cervix epithelial tissue group is of no statistical significance(P>0.05). Loss of KiSS-1 mRNA expression was correlated with clinical stage and lymph node metastasis of SCC(P<0.01, P<0.05 ), but was not correlated with age of patients and histological grade of SCC(P>0.05).2. The positive rate of metastin in normal cervix epithelial tissue, CIN, and SCC was 100 % (12/12), 78.6% (11/14) and 39.1%(18/46), respectively. There was statistical significance among there groups(P<0.01). The positive rate of SCC group was significantly less than CIN and normal cervix epithelial tissue group, difference had statistical significance(P<0.05, P<0.01). The difference between CIN and normal cervix epithelial tissue group is of no statistical significance(P > 0.05). Loss of metastin expression was correlated with clinical stage and lymph node metastasis of SCC(P<0.05), but was not correlated with age of patients and histological grade of SCC(P>0.05).3. The positive rate of MMP-9 protein in normal cervix epithelial tissue, CIN, and SCC was 8.3%(1/12), 64.3%(9/14) and 71.7%(33/46), respectively. There was statistical significance among there groups(P<0.01). The positive rate of SCC and CIN group was higher than normal cervix epithelial tissue group, difference had statistical significance(P<0.01,P<0.05). The difference between SCC and CIN group is of no statistical significance (P>0.05). High-expression of MMP-9 was correlated with lymph node metastasis of SCC(P<0.05), but was not correlated with age of patients, histological grade and clinical stage of SCC(P>0.05).4. The expression of KiSS-1 mRNA is positively correlated with metastin in cervical tissue(r_s=0.664, P<0.01), the expression of metastin is negatively correlated with MMP-9 protein in the tissue of SCC (r_s= -0.387, P<0.01)Conclusion1. KiSS-1 mRNA and metastin highly expressed in normal cervix epithelia and CIN, and low expressed in SCC. Loss of KiSS-1mRNA and metastin expression was correlated with clinical stage and lymph node metastasis of SCC. These indicated that KiSS-1 may play an important role in infiltration and metastases of SCC.2. MMP-9 protein low expressed in normal cervix epithelia, and highly expressed in SCC and CIN. High expression of MMP-9 in SCC correlated with lymph node metastasis of SCC. These indicated that MMP-9 may participate in infiltration and metastases of SCC.3. The positive correlation of expression of KiSS-1 mRNA and metastin indicated that transcription and translation of this gene could be consistent in cervical tissue. The negative correlation of expression of metstin and MMP-9 protein indicated that they may interact in the infiltration and metastasis of SCC.
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