The Expression Of The Bmi-1and OPN In Cervical Squamous Cell Carcinoma And Its Relationship With Invasion And Metastasis

Background and ObjectiveCervical cancer is the second common malignant tumor that threats to women’shealth,and its onset age becomes younger. The main factors that affect the casefatality rate and the prognosis are the invasion and metastasis of cervical cancer.In theprocess of development of cervical cancer,there are a variety of activation of cancergenes and inactivation of Tumor-suppressor genes associated with invasion andmetastasis. Therefore,treatment and prognosis judgment of cervical cancer in theclinical depends on researching the development of cervical cancer and the MolecularBiology of infiltration transfer mechanisms.In recent years, many researches havedemonstrated that epithelial-mesenchymal transition (EMT) has concerned withinvasion and metastasis of tumors derived from epithelial cells,and EMT plays animportant role in situ invasion and distant metastasis of malignant tumour，such asoral cancer, lung cancer, breast cancer, liver cancer, colon cancer, ovarian cancer,prostate cancer,etc.Expression of E-cadherin downregulation and expression ofVimentin upregulation are the main feature of epithelial-mesenchymaltransition.Proto-oncogene B-cell-specific Moloneymurine leukemia virus insertionsite l(BMI-1)) is a member of polycomb group genes family,and it plays an important role in the controlof cell proliferation、apoptosis and the Stem cell self-renewal.Manyresearches have shown that Bmi-1is upregulated in many tumors,Bmi-1has asignificant correlation with malignant transformation of tumor. Osteopontin(OPN) isa kind of Calcium-binding Phosphoprotein. A number of studies show that OPN isclosely related to invasion、metastasis and malignant transformation of tumors,andOPN gene is also known as tumor metastasis-related gene. At present,the referencesof Bmi-1and OPN in cervical cancer about the invasion and metastasis is less.In thisstudy, The subject is that examining the expression of Bmi-1、OPN and EMTmolecular markers E-cadherin, Vimentin in cervical carcinogenesis process, andanalyzed their relevance,and discussed the function of Bmi-1、OPN in the invasionand metastasis of cervical cancer.Materials and methods:1.Specimen Source:Collecting126wax samples preserved in pathologydepartment of the Second Affiliated Hospital of Zhengzhou University from June2012to July2013,which includes20cases with normal cervical tissue of totalhysterectomy because of uterine fibroids,60cases with cervical intraepithelialneoplasia(CIN) tissue (CINI、CINII and CIN III were25cases,19cases and16cases)and46cases with squamous carcinoma of the cervix without preoperativechemotherapy and postoperative pathological diagnosis.2.Experimental method: Detect the expression of Bmi-1、OPN、E-cadherin andVimentin of20cases of normal cervix tissue,60cases of CIN tissue and46cases ofcervical squamous cell carcinoma tissue using immunohistochemistry techniques,andanalyze their relationship.3.Statistical methods:SPSS17.0statistical package is used to analyze and processthe datas, comparison of qualitative data adopt the chi-square test or Fisher’s exacttest, relevance analysis using2×2paired correlation analysis. P <0.05is defined asthe significant statistical difference.Results:1.The expression of Bmi-1:Bmi-1protein is mainly located in cell nucleus ofnormal cervical、CIN and Cervical squamous cell carcinoma.The expression of Bmi-1gradually increases in normal cervical、CIN and Cervical squamous cell carcinoma, the overall is statistically different (P＜0.05)；among the comparion of normal cervixand cervical squamous cell carcinoma, CIN and cervical squamous cell carcinomadifferences are statistically significant (P＜0.05). The difference of Bmi-1expressionin CINI、CINII、CINIII is statistically significan（tP＜0.05）;among CINI and CINIIIdifference is statistically significant (P＜0.05). The expression of Bmi-1protein incervical squamous carcinoma tissues is related to patients’Clinical stage、histologicclassification、lymph node metastasis(P＜0.05).2.The expression of OPN:OPN protein is mainly located in cell cytoplasm andnucleus of normal cervical、 CIN and Cervical squamous cell carcinoma.Theexpression of OPN gradually increases in normal cervical、CIN and Cervicalsquamous cell carcinoma,the overall is statistically different (P＜0.05);among thecomparion of normal cervix and cervical squamous cell carcinoma, CIN and cervicalsquamous cell carcinoma differences are statistically significant (P＜0.05). Theoverall difference of Bmi-1expression in CINI、CINII、CINIII isn’t statisticallysignificant (P＜0.05),and the pairwise comparison differences are not statisticallysignificant (P＞0.05). The expression of OPN protein in cervical squamous carcinomatissues is related to patients’Clinical stage、histologic classification、tissue invasiondepth and lymph node metastasis(P＜0.05).3.The expression of E-cadherin: E-cadherin protein is mainly located in cellmembrane of normal cervical、CIN and Cervical squamous cell carcinoma.Theexpression of E-cadherin gradually decreases in normal cervical、CIN and Cervicalsquamous cell carcinoma, the overall is statistically different (P＜0.05); whichpairwise comparisons are statistically significant differences (P＜0.05). The overalldifference of Bmi-1expression in CINI、CINII、CINIII isn’t statistically significant (P＜0.05),and the pairwise comparison differences are not statistically significant (P＞0.05). The expression of E-cadherin protein in cervical squamous carcinoma tissues isrelated to patients’Clinical stage、 histologic grade、 invasion and lymph nodemetastasis(P＜0.05).4.The expression of Vimentin:Vimentin does not express in normal cervicaltissue,It is mainly located in the cytoplasm of CIN and Cervical squamous cellcarcinoma.The expression of Vimentin gradually increases in CIN and Cervical squamous cell carcinoma, the overall is statistically different (P＜0.05); among thecomparion of normal cervix and cervical squamous cell carcinoma, CIN and cervicalsquamous cell carcinoma differences are statistically significant (P<0.05). The overalldifference of Bmi-1expression in CINI、CINII、CINIII isn’t statistically significant (P＜0.05).and the pairwise comparison differences are not statistically significant (P＞0.05). The expression of Vimentin protein in cervical squamous carcinoma tissues isrelated to patients’Clinical stage、invasion and lymph node metastasis(P＜0.05).5.The correlation of Bmi-1、OPN、E-cadherin and Vimentin in cervicalsquamous carcinoma tissues:(1)The expression of Bmi-1is negatively correlated with E-cadherin (r=-0.531,P＜0.05),and positively correlated with Vimentin（r=0.344,P＜0.05）；(2)The expression of OPN is negatively correlated E-cadherin（r=-0.544,P＜0.05),and positively correlated with Vimentin（r=0.368,P＜0.05）；(3)The expression of Bmi-1is positively correlated with OPN（r=0.507,P＜0.05）；(4)The expression of E-cadherin is positively correlated with Vimentin（r=-0.341,P＜0.05）。Conclusion:1.The high expression of proto-oncogene Bmi-1and tumor metastasis-associatedgene OPN is closely related with cervical squamous cell carcinoma histologicalgrade, clinical stage and lymph node metastasis, which suggests that Bmi-1, OPNmay play an important role in the process of the development、invasion and metastasisof cervical squamous cell carcinoma.2. Bmi-1, OPN may be through epithelial-mesenchymal transition promoteinvasion and metastasis of cervical squamous cell carcinoma.3. The expression of Bmi-1is positive correlated to OPN,suggesting that thetwo possible synergistic invasion and metastasis of cervical cancer.