Expression Of DKK1、SFRP4and β-catenin In Human Cervical Squamous Cell Carcinoma And Their Correlation

Objective:To analyze the role and correlation of DKK1、SFRP4and β-catenin inthe occurrence and development of human cervical squamous cell carcinomaby detecting the expression of these factors in normal cervix and cervicalsquamous cell carcinoma,as well as the relationships of these factors with theclinical pathological characteristics of cervical squamous cell carcinomapatients,such as age, differentiation, depth of invasion, lymph node metastasisand clinical stage so as to evaluate the role and significance of them in theWnt/β-catenin pathway.Methods：54cases of cervical squamous cell carcinoma (SCC) and20cases ofnormal cervix(NC) which were surgically removed and certified by pathologyfrom May,2010to May,2011of the Affiliated Hospital of Chengde MedicalCollege were collected. RT-PCR was used to detect mRNA expression ofDKK1、SFRP4and β-catenin, immunohistochemical staining was used todetect protein expression of DKK1、SFRP4and β-catenin.Results：1The expression of DKK1in SCC and NC.Both mRNA and protein expression of DKK1in SCC of lowdifferentiation was significantly lower than those of moderate and highdifferentiation(P<0.01, P<0.01); Both mRNA and protein expression of DKK1in SCC of moderate and high differentiation was significantly lower than thosein NC (P<0.01, P<0.01).2The expression of SFRP4in SCC and NC.Both mRNA and protein expression of SFRP4in SCC of lowdifferentiation was significantly higher than those of moderate and high differentiation(P<0.01, P<0.01); Both mRNA and protein expression ofSFRP4in SCC of moderate and high differentiation was significantly higherthan those in NC (P<0.01, P<0.01).3The expression of β-catenin in SCC and NC.Both mRNA and protein expression of β-catenin in SCC of lowdifferentiation was significantly higher than those of moderate and highdifferentiation(P<0.01, P<0.01); Both mRNA and protein expression of β-catenin in SCC of moderate and high differentiation was significantly higherthan those in NC (P<0.01, P<0.01).4The relationships between expression of DKK1and clinicalpathological characteristics of SCC.4.1The relationships between expression of DKK1mRNA andclinical pathological characteristics of SCC.The expression of DKK1mRNA was positively correlated with lymphnode metastasis and FIGO stage. The expression of DKK1mRNA of lymphnode metastasis group was significantly lower than that of without lymph nodemetastasis group (P<0.01).The expression of DKK1mRNA of FIGO stageⅡwas significantly lower than that of FIGO stageⅠ(P<0.01).Correlations were not found between DKK1mRNA and every othercharacteristics of SCC such as age and depth of invasion(P>0.05, P>0.05).4.2The relationships between expression of DKK1protein and clinicalpathological characteristics of SCC.The expression of DKK1protein was positively correlated with lymphnode metastasis and FIGO stage.The positive expression of DKK1protein oflymph node metastasis group was lower than that of without lymph nodemetastasis group (P<0.05).The positive expression of DKK1protein of FIGOstage Ⅱ was significantly lower than that of FIGO stageⅠ(P<0.01).There were no relationships between DKK1protein and every othercharacteristics of SCC such as age and depth of invasion(P>0.05, P>0.05).5The relationships between expression of SFRP4and clinicalpathological characteristics of SCC. 5.1The relationships between expression of SFRP4mRNA and clinicalpathological characteristics of SCC.The expression of SFRP4mRNA was positively correlated with lymphnode metastasis and FIGO stage.The expression of SFRP4mRNA of lymphnode metastasis group was significantly higher than that of without lymphnode metastasis group (P<0.01).The expression of SFRP4mRNA of FIGOstage Ⅱ was significantly higher than that of FIGO stageⅠ(P<0.01).Correlations were not found between SFRP4mRNA and every othercharacteristics of SCC such as age and depth of invasion(P>0.05, P>0.05).5.2The relationships between expression of SFRP4protein and clinicalpathological characteristics of SCC.The expression of SFRP4protein was positively correlated with lymphnode metastasis and FIGO stage.The positive expression of SFRP4protein oflymph node metastasis group was higher than that of without lymph nodemetastasis group (P<0.05).The positive expression of SFRP4protein of FIGOstage Ⅱ was higher than that of FIGO stageⅠ(P<0.05).There were no correlations between SFRP4protein and every othercharacteristics of SCC such as age and depth of invasion(P>0.05, P>0.05).6The relationships between expression of β-catenin and clinicalpathological characteristics of SCC.6.1The relationships between expression of β-catenin mRNA andclinical pathological characteristics of SCC.The expression of β-catenin mRNA was positively correlated with lymphnode metastasis and FIGO stage.The expression of β-catenin mRNA of lymphnode metastasis group was significantly higher than that of without lymphnode metastasis group (P<0.01).The expression of β-catenin mRNA of FIGOstage Ⅱ was significantly higher than that of FIGO stageⅠ(P<0.01).Correlations were not found between β-catenin mRNA and every othercharacteristics of SCC such as age and depth of invasion(P>0.05, P>0.05).6.2The relationships between expression of β-catenin protein andclinical pathological characteristics of SCC. The expression of β-catenin protein was positively correlated with lymphnode metastasis and FIGO stage.The positive expression of β-catenin proteinof lymph node metastasis group was significantly higher than that of withoutlymph node metastasis group (P<0.01).The positive expression of β-cateninprotein of FIGO stage Ⅱ was higher than that of FIGO stageⅠ(P<0.05).There were no correlations between β-catenin protein and every othercharacteristics of SCC such as age and depth of invasion(P>0.05, P>0.05).7The relationships among DKK1、SFRP4and β-catenin.There was negative correlation between the expression of DKK1and β-catenin in SCC and NC, both mRNA levels and protein levels (r=-0.869,P<0.01; r=-0.517, P<0.01). There was positive correlation between theexpression of SFRP4and β-catenin in SCC and NC, both mRNA levels andprotein levels (r=0.896, P<0.01; r=0.821, P<0.01). There was negativecorrelation between the expression of DKK1and SFRP4in SCC and NC, bothmRNA levels and protein levels (r=-0.871, P<0.01; r=-0.547, P<0.01).Conclusion：1The low expression of DKK1, the high expression of SFRP4and β-catenin may play an important role in the occurrence of SCC.2The expression of DKK1, SFRP4and β-catenin was significantlycorrelated with lymph node metastasis and FIGO stage. These indicated thatthey may play an important role in the metastasis and development of SCC.3There was negative correlation between the expression of DKK1and β-catenin in SCC and NC. There was positive correlation between theexpression of SFRP4and β-catenin in SCC and NC. There was negativecorrelation between the expression of DKK1and SFRP4in SCC and NC.These suggested that DKK1might play a negative role in the Wnt/β-cateninpathway,the low level or disappearance of DKK1might activate theWnt/β-catenin pathway in SCC,in the end led to the occurrence of SCC.Thehigh level of SFRP4might play an important role in activating theWnt/β-catenin pathway in SCC and the occurrence and development of SCC.β-catenin was the sign in activating the Wnt/β-catenin pathway.