| Colonic cancer is a common gastrointestinal cancer,which ranks the third highest incidence of cancer in the world and the fifth in cancer mortality.Including colon cancer,most tumors may probably be cured at the earliest stages of cancer by surgery,but over 90%of colonic cancer patients can not get the timely and effective treatment as a result of local recurrence and distant metastasis.Colonic cancer is one of the major causes of cancer-related death,and in most regions of of China it has become he highest rate of rising of malignant tumor,therefore colonic cancer has got the major concern of our government and people.Although the treatment of colonic cancer has been enriched continuously in recent years,but the timely and effective treatment has not appeared yet,therefore,it is important for us to study the molecular mechanism of invasion and metastasis of colonic cancer and find more valuable tumor markers,which will benefit the treatment and prognosis of patients of colonic cancer.SMYD3(SET and MYND domain-containing protein-3)is a protein,which can methylate chromosomal histone H3(H3K4)two or three times,and the function plays an important role in the process of SMYD3regulating the target gene transcription.As an important member of RNA polymerase complex,SMYD3 can methylate histone H3(H3K4),regulate the transcriptional of RNA Pol-II,and interact with the sequence-specific binding proteins,finally affect the target oncogenes and the suppressor gene of tumor,cell cycle regulatory proteins,the genes related cells adhesion,and the signal transduction related genes,etc.Finally SMYD3 can inhibite the cells of cancer apoptosis and promot the proliferation and invasion of the cells.SMYD3 can also regulate the transcriptional regulation of genes which involve in the process of epithelial mesenchymal transition(EMT),then invasion and metastasis of the cells of cancer can become stronger via EMT,which result in the local spread and distant metastasis of the tumor cells.Therefore,exploring the role and mechanism of SMYD3 in the progress of colonic cancer is far-reaching significance.LOXL2(LOX-Like,Lysyl Oxidase-2)is a member of LOX(The Lysyl Osidase)family and the gene is localized in human chromosome8p21.2-p21.3.LOXL2 is a copper-dependent secreted ammonia oxidase,and it can catalyze the oxidative deamidation of amino groups in lysine residues of specific peptidyl groups,then promote the cross-linking of covalent proteins in the extracellular matrix(ECM),and stabilize the elastic and collagen fibers in ECM.Therefore,LOXL2 plays an important role in the process of the cancer cells in adhesion,migration and epithelial-mesenchymal transition.As the latest regulator of EMT,LOXL2 can also interact with Snail to promote EMT,finally promote the migration and metastasis of the cancer cells.Therefore,studying the specific mechanism of LOXL2 has great significance for the development of the new targeted drugs for colonic cancer.EMT(epithelial mesenchymal transition)is the process of the epithelial cells transform into the stromal cells.The changes of the inside and outside environment of the cancer cells result in the missing of important components junction of the epithelial cells,and the activation of interstitial cell-specific protein,which promote the invasion and metastasis of the tumor cells finally.EMT has become the key event in the progression of tumor by promoting the proliferation and metastasis of the tumor cells.And the decreasing of E-cad gene expression is the key step of EMT.E-cad distributes in the membrane surface of the cells in the form of dimer,then form the multimers by the identification of adjacent cells,which plays an important role of the adhesion and communication between cells.The decreasing of E-cad expression lead to the loss of the adhesion between cells,which result in the increased activity of the tumor cells,prompt the tumor cells through the basement membrane,and increase the ability of tumor cells in differentiation and invasion.Therefore,E-cad plays an important biological role in the progress of malignant tumor such as proliferation,differentiation,migration and metastasis.Objective:By detecting the expression of SMYD3,LOXL2 and E-cad in colonic cancer and paracancerous tissues,we investigated the relationship between the expressions of SMYD3,LOXL2 and E-cad in colonic carcer and the clinicopathological features,and explored the correlation of SMYD3,LOXL2and E-cad in the progress of colon cancer,which would provide the guidance for the effective and timely clinical treatment and prognosis of patients with colonic cancer.Methods:72 cases of colon cancer tissues paraffin blocks and 36 cases of paracancerous tissues paraffin blocks were collected,which were excisied by surgery and had been diagnosed of pathological method accurately,and all cases never recieved any anti-tumor treatment before surgery.The expressions of SMYD3,LOXL2 and E-cad in colonic cancer tissues was detect by immunohistochemistry MaxVision staining,and whether the expressions of SMYD3,LOXL2 and E-cad were related with age,sex,tumor differentiation,TNM stage,depth of invasion and lymph node metastasis were analyzed.The data collected was analyzed by SPSS 19.0,the count data by test ofχ~2,and correlation analysis data by Spearman’s rank.α=0.05 was used as the inspectful standard and P<0.05 was considered statistically significant.Results:1.In colonic cancer tissues and adjacent tissues,the expressions of SMYD3,LOXL2 and E-cad were observed.The expression of SMYD3 was mainly located in the nucleus of cancer cells,meanwhile its expression was also observed in the cytoplasm;the expression of LOXL2 was mainly observed in the cytoplasm;the expression of E-cad was mainly located in the membrane.The positive rates of SMYD3 and LOXL2 in colonic cancer tissues were 59.7%(43/72)and 75.0%(54/72)respectively,which were higher than those in paracancerous tissues 16.7%(6/36)and 13.9%(5/36),meanwile the difference(χ~2=17.950,P<0.05;χ2=36.162,P<0.05)was statistically significant.2.In colonic cancer the expressions of SMYD3,LOXL2 and E-cad were correlated with lymph node metastasis,TNM stage and the depth of invasion(P<0.05),and the correlation with age,sex and differentiation was not observed(P>0.05).3.In colonic cancer a positive correlation between the expressions of SMYD3 and LOXL2 was observed(r=0.376,P<0.05),the expression of SMYD3 and LOXL2 were negatively correlated with the expression of E-cad respectively(r=-0.31,P<0.05;r=-0.54,P<0.05).Conclusion:The positive expressions of SMYD3 and LOXL2 in colonic cancer tissues was significantly higher than those in paracancerous tissues,while the positive expression of E-cad in cancerous tissues was lower than that in paracancerous tissues,suggesting that SMYD3,LOXL2 and E-cad were closely related to the development of colonic cancer.The expressions of SMYD3,LOXL2 and E-cad in colonic cancer were related with lymph node metastasis,TNM stage and depth of infiltration,meanwile the deeper depth of penetration,with lymph node metastasis,the later TNM staging of cases with the higher positive expressions of SMYD3 and LOXL2,but with the lower expression of E-cad,which suggest that SMYD3,LOXL2 and E-cad were associated with poor prognosis and malignancy of colonic cancer.The expressions of SMYD3 and LOXL2 were correlated positively,but the expression of E-cad was negatively correlated with the expressions of SMYD3 and LOXL2,which suggesting they were related to the EMT process,and combined detection of them could further provide the theoretical basis for the invasion and metastasis mechanism of colon cancer patients. |
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