Expressions And Clinical Significances Of E-cadherin,?-catenin And MMP-7 In Oral Squamous Cell Carcinoma

Objective: Oral squamous cell carcinoma(OSCC)is one of the most common malignant tumors of the head and neck with the characteristic of high grade of malignancy and clinical symptoms such as erosion,ulcers,bleeding and restricted tongue movement,which seriously affects patients' daily lives.E-cadherin(E-cad)is a calcium-dependent transmembrane glycoprotein and plays an important role in maintaining the polarity and integrity of normal epithelium.The low expression of E-cad reduces the adhesive power of homotypic cells and promotes the occurrence and development of most tumors.?-cat is a multifunctional protein and a key effector molecule of the classic Wnt signaling pathway.It participates in the regulatation of growth and differentiation of the normal cells.Its abnormal expression can activate most proto-oncogenes in the body and participate in the development of tumors.The function of E-cad is inseparable from ?-cat,the two must form an E-cad / cat complex to play a role.Matrix metalloproteinase-7(MMP-7)is a proteolytic enzyme and can mediate the progression of tumor by degrading extracellular matrix and basement membrane macromolecules and other ways.MMP-7 is one of the key downstream target genes of Wnt/?-cat,and can hydrolyze the extracellular structure of E-cad,so that its intercellular adhesion function is lost.E-cad,?-cat and MMP-7 can interact in most tumors and mediate development and progression of tumor in common.However,there are few studies on the relationships and their correlations between E-cad,?-cat and MMP-7 in OSCC at present.In this experiment,we adopt the methods of real-time quantitative polymerase chain reaction(qRT-PCR)and immunohistochemistry(IHC)to detect the expressions of E-cad,?-cat and MMP-7 in OSCC at the gene level and protein level by collecting normal oral mucosal tissues,fresh OSCC tissues,adjacent tissues of OSCC,and OSCC pathological sections and Simultaneously analyzed the relationships between the expressions of three proteins and the clinicopathological factors of patients.We analyzed the relationships between the expressions of E-cad,?-cat and MMP-7 and the development and progression of OSCC to provide new ideas for clarifying the mechanism of occurrence,diagnosis and treatment of OSCC.Methods: 1.Collect Six cases of fresh OSCC tissues,Six cases of para-carcinoma OSCC tissues and Six cases of normal oral mucosa tissues that all meet the standards.Detect the expressions of mRNA of E-cad,?-cat and MMP-7 in the three tissues respectively by the method of qRT-PCR;2.Select 10 cases of fresh normal oral mucosa tissue and 30 cases of OSCC paraffin tissue block that meets certain criteria,40 cases in total.The method of Hematoxylin and eosin staining(HE)is used for pathological classification,and the method of immunohistochemical SP is used to detect the expressions of E-cad,?-cat and MMP-7 protein in normal oral mucosa and OSCC.Simultaneously analyze the relationships between the expressions of three proteins and the clinicopathological factors of patients.Results: 1.qRT-PCR results: The mRNA relative expressions of E-cad and ?-cat were highest in the normal group.Compared with the normal group,the mRNA relative expressions of E-cad and ?-cat in the group of OSCC were respectively decreased by 0.58 multiple and 0.76 multiple,and it was respectively decreased by 0.68 multiple and 0.53 multiple in the group of para-carcinoma of OSCC,and the differences of the mRNA expressions of E-cad and ?-cat in two groups showed statistical significance(P <0.05).Compared with the group of para-carcinoma of OSCC,the differences of the mRNA expressions of E-cad and ?-cat in the OSCC group respectively showed no statistical significance(P >0.05).MMP-7 mRNA was no expressed in the normal group,but it were strongly positive expressed in both the group of OSCC and the group of para-carcinoma of OSCC,and the mRNA relative expression level of MMP-7 in the group of para-carcinoma of OSCC was the highest(up to 6.90 multiple compared with the OSCC group).The differences of the mRNA expressions of MMP-7 in the OSCC group and in the group of para-carcinoma of OSCC showed statistical significance(P>0.05).2.HE staining results: Conventional HE staining was used to pathological grade for normal oral mucosa tissues and paraffin tissue blocks of OSCC.Forty pathological sectionsare were analyzed by two senior pathologists and included ten cases of normal oral mucosa tissues,ten cases of poorly differentiated OSCC,ten cases of moderately differentiated OSCC and ten cases of highly differentiated OSCC;3.IHC staining results: In normal oral mucosa tissues,E-cad and ?-cat were strongly expressed on the epithelial cell membrane,and MMP-7 was no expressed.As the differentiated degree of OSCC decreases:the expressions of E-cad were gradually down-regulated and even disapeared on the cell membrane;the expressions of ?-cat were gradually down-regulated and even disapeared on the cell membrane,and were gradually appeared in some cytoplasmic or some nucleus;the expressions of MMP-7 were gradually up-regulated in cytoplasm.The differences of the expressions of the three proteins were statistical significance among the four groups(P <0.05).The expressions of the three proteins all were related to the differentiated degree of OSCC(P <0.05);4.The relationships between the expressions of three proteins and the clinicopathological parameters of patients: In OSCC,the expressions of E-cad in the non-lymph node metastasis group and in the non-infiltration group both were higher,and the differences between the two groups respectively showed statistical significance(P <0.05).While the differences of the expressions of E-cad in the groups of patients' age,patients' gender,smoking and drinking,tumor size,clinical stage and recurrence(following-up from 3 to 30 months)respectively showed no statistical significance(P> 0.05).There was no statistical significance in the differences of the expressions of ?-cat and MMP-7 in each group(P> 0.05).Conclusion: In OSCC,the expressions of E-cad,?-cat and MMP-7 is all closely related to the differentiated degree of OSCC.E-cad,?-cat and MMP-7 may play a certain synergistic role in the process of OSCC and promote the occurrence and development of OSCC.