Expression And Significance Of Homeobox Protein SIX6 And Matrix Metalloproteinase-14 In Cervical Squamous Cell Carcinoma And Squamous Intraepithelial Lesions

Purpose:To investigate the expression and clinical significance of Six6 and MMP14 in cervical squamous cell carcinoma,and to analyze their correlation,and further explore the mechanism of SIX6 and MMP14 in the occurrence and development of cervical squamous cell carcinoma,so as to provide theoretical basis for prognosis judgment and treatment.Methods:56 cases of cervical squamous cell carcinoma were collected(13 cases of keratotic type,43 cases of non-keratotic type;43 cases of FIGO stage Ⅰ,13 cases of FIGO stage Ⅱ;7 cases of tumor maximum diameter<2cm,≥2cm but<4cm 36 cases,13 cases of ≥4cm;10 cases of invasion depth ≤1/2 muscle layer,46 cases of>1/2 muscle layer;26 cases with vascular invasion,30 cases without vascular invasion;14 cases with lymph node metastasis and 42 cases without lymph node metastasis),60 cases of cervical squamous cell intraepithelial lesions(20 cases of CIN Ⅰ,20 cases of CIN Ⅱ and 20 cases of CIN Ⅲ),and 20 cases of normal cervical tissue.Immunohistochemical staining of Six6 and MMP14 was performed in all cases to observe the expression and difference in cervical squamous cell carcinoma and squamous cell intraepithelial lesions,tumor maximum diameter,tumor invasion depth,vascular invasion and lymph node metastasis,and the correlation analysis was performed.Results:The positive expression rates of SIX6 and MMP14 proteins in cervical squamous cell carcinoma specimens were higher than that in cervical squamous cell intraepithelial lesions.The positive expression rate of SIX6 in SCC was 60.71%,and the negative expression rate of SIX6 in CINⅠ grade was 10.00%;the positive expression rate of SIX6 in CIN Ⅱ grade was 33.33%;the positive expression rate of SIX6 in CIN Ⅲ grade was 43.33%,the difference was statistical significance(P<0.05).The positive expression rate of MMP14 in SCC was 62.50%,the positive expression rate of CIN Ⅰ grade was 11.67%,the positive expression rate of MMP14 in CINⅡ grade was 35.00%;the positive expression rate of MMP14 in CIN Ⅲgrade was 41.67%,the difference was statistically significant(P<0.05).The expression rates of SIX6 and MMP14 proteins in keratinizing SCC were both 69.23%,and the expression rates of SIX6 and MMP14 proteins in non-keratinizing SCC were 58.14%and 60.47%,with no significant difference(P>0.05).The expression rates of SIX6 and MMP14 proteins were both 92.31%in FIGO stage Ⅱ,which were higher than those in FIGO stage Ⅰ(respectively:47.62%,50.00%),and the difference was statistically significant(P<0.05).In the tumors with the largest tumor diameter<2cm,the expression rates of SIX6 and MMP14 proteins were both 28.57%,and the expression rates of SIX6 and MMP14 proteins were both 61.11%in the cases with the largest tumor diameter ≥2cm but<4cm.In the tumors with the largest diameter ≥4cm,the expression rates of SIX6 and MMP14 protein expression rates were 76.92%and 84.62%,respectively,and the difference was not statistically significant(P>0.05).The expression rates of SIX6 and MMP14 proteins were 69.57%and 71.74%,respectively,in the cases with infiltration depth>1/2 of the myometrium.It was significantly higher than the cases with invasion depth ≤1/2 of the muscle layer(both 20.00%),and the difference was statistically significant(P<0.05).In the cases with vascular invasion,the expression rate of SIX6 and MMP14 proteins were 100%and 96.15%,respectively,which were significantly higher than the cases without vascular invasion(respectively:20.00%,30.00%),and the difference was statistically significant(P<0.05);The expression rates of SIX6 and MMP14 proteins were both 100%in cases with lymph node metastasis,which were higher than those without lymph node metastasis(respectively:47.62%,50.00%),and the difference was statistically significant(P<0.05).It is suggested that the expression of SIX6 and MMP14 was closely related to tumor stage,depth of invasion,vascular invasion and lymph node metastasis.The expressions of SIX6 and MMP14 were positively correlated in CIN and SCC.Conclusion:The protein expression rates of SIX6 and MMP14 are related to the severity of cervical squamous cell disease,suggesting that SIX6 and MMP14 may be involved in the pathogenesis of cervical squamous cell carcinoma.The protein expression rates of SIX6 and MMP14 were not significantly different from histological types and tumor size,but were positively correlated with FIGO stage,vascular invasion,depth of invasion and lymph node metastasis.It was speculated that the protein expression of SIX6 and MMP14 promoted the occurrence and development of cervical cancer and could be used as one of the indicators of clinical prognosis.The expressions of SIX6 and MMP14 were positively correlated,and the two may have a positive synergistic effect.