| BackgroundColorectal cancer is one of the most common gastrointestinal tumor, its morbidityand mortality rates are increasing year by year, and it threats to the human healthseriously.TNM staging which is widely used at present is to determine the main basisof the CRC prognosis, but clinical and pathologicalstagingis insufficient to predict therisk of recurrence and metastasis of stage II CRC.Though stage II CRC is in earlystage of colorectal cancer,but the prognosis is very different,about20%of patientswho is postoperative occur recurrence and metastasis.Studying risk factors andmolecular markers of staget II CRC can add the deficiencies of the stagingsystem,and provide a theoretical basis to the cure which is on account of biologicalcharacteristics of tumor individual.Galectin-3involved in regulating tumor cell growth, apoptosis, adhesion,angiogenesis and tumor invasion and metastasis process,it palys a important role inthe progression and developmenet of CRC.We have drawed the conclusion that usinga competitive inhibitor LCP of galectin-3ligand can close surface of tumor cells,andprevent the development of tumor cells and inhibition of metastasis in vitro and invivo experiments.That galectin-3participate in invasion and transfer of tumor may be have ralation to cell-cell and cell-matrix adhesion, angiogenesis and othermechanisms,but its specific role in the recurrence and metastasis in CRC is unclear,and there is no any reports of the relastionship between galectin-3and II of CRCrecurrence and metastasis in clinical studies.Tumor invasion and metastasis involve multiple mechanisms, in which the EMTis an early event in tumor invasion and metastasis.When EMT occured, intercellularconnection failure, cell migration ability increases,cancer cells acquire invasiveness,make tumor cells metastasis. Activation of downstream target genes of the Wnt/beta-catenin signaling pathway can cause the EMT, galectin-3in the regulation of theWnt/beta-catenin signaling pathway plays an important role,the effect and relationbetween galectin-3and EMT in CRC recurrence and metastasis is not clear,galectin-3indirectly affect the EMT by regulating the Wnt/β-catenin pathway needs to befurther confirmed.The aim of this retrospective study was to determine the risk factors forrecurrence and metastasis in stage II CRC and to explore the expression ofgalectin-3、 E-cadherin、vimentin in the stage II CRC and its potential clinicalsignificance, in order to help the screening of stage II CRC patients with high-riskfactors, Our recearch may provide the theoretical basis for further illuminating themolecular mechanism of colorectal cancer development and finding the new targetsfor diagnosis of colorectal cancer and to guide the clinical individual therapy.ObjectiveTo explore the expression of galectin-3, E-cadherin and vimentin in stage II CRCtissues and its clinical significance. Investigate the correlations beteeenclinicopathologic factors and the recurrence, metastasis、prognosis in stage II CRC.Investigate the role of galectin-3and EMT in stage II CRC.MethodsWe retrospectively study the consecutive cases of Stage II colorectal cancer which had undergone radical surgery from2004to2008in Affiliated Tumor Hospitalof Guangzhou Medical College. Threre are117patients included in the study andusing the mocroarray immunohistochemical technique to detect the expression ofgalectin-3,E-cadherin and vimentin,applying statistical methods to analysis theexperimental results. In addition to select the eight cases which were colorectal cancerof stageⅡ patients with colorectal tumors and matched normal tissue paraffinembedded samples as controls in Affiliated Tumor Hospital of Guangzhou MedicalCollege from January2011to November2011.All statistical analysis were performedusing the SPSS13.0statistica sofewere package.The Chi-square test, Fisher’s exact test were used to assess the relation betweenthe proteins expression and clinicopathological parameters; Chi-square test andlogistic regression were used to evaluate the variables as potential risk factors forrecurrence and metastasis;Correlation between galectin-3and E-cadherin、vimentinwere analysed by using the Spearman rank correlation coefficient analysis; Tworelated sample Wilcoxon non-paramentric test were usde to compare the proteinexpression level between8cases of paraffin-embeded tissue sections of stage II CRCand paired adjacent non-neoplastic tissues;Overall survival curves between subgroupsdivided accordding to the protiens expression levels were drawn by using theKaplan-Meier method,and significant differences among subgroups were comparedbuy using the log-rank analysis;Multivariate analysis were performed using Coxproprortional hazards model to identify independent prognostic factors.α=0.05(two-sided) as the difference level,and P<0.05was considered indicative ofstatistical significance.Results1. Galectin-3was mainly expressed in the cytoplasm, the expression rate is81.2%, itsexpression is associate with tumor size, degree of differentiation and the level ofpreoperative serum CEA (P <0.05), the high expression of Galectin-3is significantlyassociated with the larger diameter of the tumors, the poor differentiation and the higher level of preoperative CEA.2.E-cadherin which is in adjacent normal tissue was mainly expressed in the cellmembrane, and mainly expressed in cytoplasm when it is in tumor tissue. Theexpression rate was44.4%in tumor tissue, its higher expression is significantlyassociated with the well differentiation.3.Vimentin was expressed in stroma,the expression rate was76.1%, its expression issignificantly associated with the higher T stage.4, Univariate analysis showed that the recurrence and metastasis were associated withtumor location、the sampling of lymph nodes, T stage, whether postoperative adjuvantchemotherapy, preoperative serum CEA level, expression of galectin-3and vimentin.Multivariate analysis showed that the recurrence and metastasis were significantlyassociated with preoperative CEA level, the sampling of lymph nodes and galectin-3expression (P <0.05).5, Univariate analysis showed that prediction prognostic was associated with tumorlocation,tumor size,the sampliing of lymph nodes, T stage, preoperative serum CEAlevel, whether postoperative adjuvant chemotherapy, expression level of galectin-3and vimentin.Multivariate analysis showed that prediction prognosis was significantlyassociated with preoperative serum CEA level, T stage (P <0.05).6,Galectin-3expression is negatively correlated with expression of E-cadherin (r=-0.218, P=0.018), but galectin-3expression is not correlated with vimentinexpression(r=0.172, P=0.064).7, Galectin-3and vimentin expression in tumor tissue were significantly higher thanin adjacent normal tissues, E-cadherin expression in tumor tissue is lower than inadjacent normal tissues.Conclusions1,In stage II colorectal cancer tissues,the high expression of galectin-3was associatedwith tumor size, differentiation, preoperative serum CEA level, recurrence andmetastasis and indicated a poor prognosis.Therefore galectin-3may be used as a molecular marker to predict the recurrence and metastasis of stage II colorectalcancer.2,In stage II colorectal cancer tissues, vimentin was expression in stroma,the highexpression of vimentin was associated with metastasis and indicates a poorprognosis. |
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