| Colon cancer posses higher rate in several malignant diseasesis which is the highest incidence of digestive system in the world.In China,the incidence and mortality rates of colon cancer are on the rise.A number of studies have shown that the reason of colon cancer whose cure rate is low,mortality is high is attributable to metastasis.While the development of colon cancer is a comprehensive and complex pathological process that is referred to multi-factor,multi-stage.As a result,it is a difficult problem that to control metastasis to overcome.However,with the discovery of EMT and in-depth research in cancer,it is found that EMT is closely related to the invasion and early metastasis of many tumor cells including colon cancer.Therefore,the molecular level,connected with EMT,can be used to be an effective way to further improve the survival rate and improve the prognosis of colon cancer patients.As a member of the homologous box gene family,homologous box gene 1(Six1)can specifically regulate the expression of downstream genes by binding to specific parts of DNA.It plays a key role in the process of cell proliferation,differentiation,adhesiveness,metastasis and tissue development and so on.EMT has been to put forward as a molecular event thirty years ago.It refers to a process of the polar epithelial cells turn into interstitial cells who have the ability to metastasize in the case of some specific pathological or physiological conditions.A large number of studies have shown that,it is inseparable with the primary infiltration and secondary metastasis in most tumors.With the continuous intensive study,more and more essential factors and pathways,EMT-related,are constantly discovered and improved.Six1 protein is one of the hot-point transcriptional regulators of EMT-related molecules in recent years.It has indicated that it not only participates in the course of embryogenesis and organ differentiation,and regulates cell cycle progression,but also promotes the initiation and metastasis of cancer cell.It overexpresses in tumor,it takes part in the procedure of development and progression in tumor,through the induction of cell proliferation,promoting metastasis which depend on EMT,inhibition of apoptosis and other processes.Forkhead box protein C2(FOXC2),also known as Mesenchyme forkhead protein 1(MFH1),is a member of the forkhead box protein family which posseses the similar DNA binding domains,and it plays an important role in the process of DNA transcription.FOXC2 is one of the important regulators of EMT.It has been found that it can induce the expression of other transcription factors(Twist,Snail,TGF-β,etc.),and it can induce its own expression highly in epithelial cells.It can also regulate the expression of matrix metalloproteinase2(MMP-2)and matrix metalloproteinase-9(MMP-9)at the same time.Further more,it can assist to provide the basis that can infiltrate adjacent tissues and metastasize in distant organs for tumor cells.E-cadherin(E-cad)is widely distributed on the surface of various epithelial cells,and it is very important molecule that can remain the integrity and polarity of the cell morphology and structural,which can promote the adhesion between epithelial.Meanwhile,it is an important agent to regulate the adherency and communication between cells as well as cell and matrix.It may lead cell to lost polarity and adhesive capacity be decreased that to lost the expression and function f E-cad,which make epithelial cells show the characteristics of non-epithelial cells.Studies discovered that the low expression of E-cad was common in the process of EMT happened in epithelial cells.The deletion of E-cad in tumor cells plays a causal role in the transformation of malignant phenotype.Therefore,it is the most significant features of EMT that down-regulation of E-cad.Objective:To investigate the expression of Six1,FOXC2 and E-cad in colon carcinoma and normal tissue.To unveil the correlation between the expression of them and clinicopathologic features,and the relationship between each other in the course of development and progression in cancer.Six1 and FOXC2 lay a new theoretical foundation for tumor development and treatment of new targets.Detecting the three protein together can guide clinical prognosis.Methods:To collect colon tissue that were treated with surgical resection and pathological diagnosis,which includes 70 cases of colon adenocarcinoma and 35 cases of normal ones.All patients have not received radiotherapy,chemoth-erapy,or particle implantation before the operation.Immunohistochemical staining was used to messure the expression of Six1,FOXC2 and E-cad in colorectal carcinoma.And analyze the relationshipbetween them and gender,measurement of tumor,lymph node metastasisand so on.SPSS 19.0 software was used for data processing.The categorical data were analyzed by χ2 test and rank-sum test.The correlationwas analyzed by Spearman correlation test.α=0.05 as the inspection standard and P<0.05 was considered statistically significant.Results:Immunohistochemistry results1.Six1,FOXC2 and E-cad were expressed in colon carcinoma an dnormal colon tissues,but the level is different.Six1 and FOXC2 positiv estaining were mainly located in the cytoplasm,and the positive express ion rate in colorectal cancer tissues were respectively 82.9%(58/70)an d74.3%(52/70),which both were evidently higher than that in ordinar yones,which were 20.0%(7/35)and 22.9%(8/35).The discrepancy wereb oth statisticallyevident(χ2=39.092,P=0.000;χ2=25.200,P=0.000).E-cadpo sitive staining was mainly located in the cell membrane,the positive rat eof the expression in colon cancer tissue was 21.4%(15/70).which was significantly lower than that in normal colonic tissues(80.0%,28/35).The discrepancy was statisticallyevident.(χ2=33.103,P= 0.000)2.The expression level of the three in colon cancer had no signifi cant correlation with the gender,age,measurement of tumor and different iation,the difference didn’t have statistically significance(P>0.05),while there have some correlation with late TNM staging,lymph node invaded and invasion in deep,the discrepancy was evident.(P<0.05).3.In colon cancer,the expressions of Six1 and FOXC2 were positive correlated(r = 0.426,P <0.01);the expressions of E-cad and Six1,FOXC2 were both negative correlated(r=-0.480 P<0.05,r=-0.728,P<0.05),all the differences were statistically significant(P<0.05).Conclusion:The positive expression rates of Six1 and FOXC2 in colon cancer tissues were significantly higher than those in normal colon tissues.While expression rate of E-cad is lower in in colon.And their expression level in colon cancer was significantly correlated with the depth of invasion,lymph node metastasis and TNM staging.The deeper the depth of invasion,the higher the positive rate of them,The deeper the infiltration depth,lymph node metastasis,TNM staging later,the higher the positive rate,suggesting that the three is possibly related to the malignant behavior of colon cancer and prognosis.they may be a sensitive index to determine the invasion and metastasis of colon cancer cells.There was a positive correlation between the expression of Six1 and FOXC2 and the negative correlation between E-cad and the two former respectively.Combined detection of these three genes in colon cancer may offer a theoretical basis for EMT which led to tumor invasion and metastasis,and searching new targets for treatment.And to lay a theoretical foundation for further research on the clinical prognosis of patients with colon cancer... |
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