| Background CRC is one of the most common malignancies and remains the third leading cause of cancer-related deaths worldwide.The metastasis and recurrence are predominant cause of poor survival of CRC patients.Epithelial-mesenchymal transition(EMT)is a key step in tumor invasion and metastasis.The epithelial-mesenchymal transition(EMT)was found to play pivotal role during tumor invasion,metastatic spread and acquisition of therapeutic resistance,inducing stem cell properties,preventing apoptosis and senescence;Recent years,adequate evidence has shown that abnormal activation of epithelial to mesenchymal-transition(EMT)contributes to tumor recurrence and metastasis in colorectal cancer(CRC).MARVEL transmembrane domain-containing family(CMTM)is a family of proteins drawn in multiple malignancies.CMTM3 is a member of this family and has been identified as a potential tumor suppressor gene.We explored the expression of CMTM3 and the EMT-related markers in colorectal cancer using immunohistochemistry(IHC).The associations of CMTM3 expression with the clinicopathological characteristics of CRC,especially prognostic status,were further evaluated.Material and methods A cohort of 130 patients with colorectal carcinoma was recruited from the First Affiliated Hospital of Soochow University between January 2008 and December 2009.Formalin-fixed tumor tissues were used for immunohistochemistry(IHC),including tumor samples and matched adjacent non-tumor tissues.Detailed clinicopathological information was recorded,including each patient’s gender,age,tumor size,tumor location,tumor differentiation,metastasis status and TNM stage.The association of CMTM3,E-cadherin and vimentin expression and the clinicopathological parameters were tested using chi-square test or Fisher’s exact test.Spearman’s rank correlation test was performed to analysis the correlations between the expression of CMTM3,E-cadherin and vimentin.For survival analysis,survival curves were calculated by the Kaplan-Meier method,the differences between the groups were analyzed by the log-rank test.For univariate and multivariate analysis,the Cox proportional hazards model was used to determine prognostic significance.P value less than 0.05 was validated as the statistical significance.All statistical analyses were performed with SPSS 19.0 softwareResults1.The expression levels of CMTM3 and EMT molecules in CRCOf the 130 CRC samples,59 samples(45.38 %)exhibited high expression level of CMTM3 staining and 57 samples(43.84%)exhibited high expression level of E-cadherin staining.In contrast,vimentin showed high expression 85/130(65.4%)in tumor tissues.The expression levels of CMTM3,E-cadherin,and vimentin in CRC samples are significantly different from that in adjacent normal tissues(P<0.05).2.Correlation of CMTM3,and EMT molecules expression with clinicopathological features in CRCThe expression level of E-cadherin was closely correlated with T stage,lymph node metastasis,distant metastasis and TNM stage(p <0.05).CMTM3 and vimentin were found to be significantly associated with T stage,distant metastasis and TNM stage(p<0.05),rather than with lymph node metastasis(p>0.05).However,other clinical features,such as gender,age,tumour size,location and pathologic differentiation,were no associated with CMTM3,E-cardherin,and vimentin expression(P>0.05)3.CMTM-3 and EMT-related proteins were significantly associated with the overall survival of CRC patientsThe patients with CMTM3 and E-cadherin negatively staining showed poorer overall survival than those with positively staining(p<0.05),while higher level of vemintin were significantly associated with poorer OS(p<0.05).Moreover,further investigation by multivariate Cox analysis showed that,rather than TNM and Lymph node metastasis,CMTM3 status(p = 0.013)was an independent risk factor for patients with CRC(p<0.05)survival,respectively.4.Association of CMTM3 with Expression of EMT MarkersThe expression levels of CMTM3 were postivately with E-cadherin expression(r = 0.253,P < 0.05)and negatively related with vimentin expression(r =-0.506,P < 0.05)in clinical CRC samples.ConclusionOur results strongly suggested that the low CMTM3 expression was significantly correlated with tumor pathogenesis and may serve as a novel prognostic biomarker of CRC.Moreover,CMTM3 may promote invasion and metastasis by modulating EMT markers vimentin and E-cadherin. |
