The Expression Of MMP-9 And TIMP-1 In The Tissue And Serum Of Colorectal Cancer And Its Clinical Significance

Background:Colorectal cancer is one of the most common tumors in the clinical practice.As with the improvement in living standards,changes in food structure and increase in life pressure,the incidence of colorectal cancer in our country was on the rise in recent years.It is hidden,dangerous and often observed in the middle-late stage when its clinical symptoms arrived in,which brought great difficult to its diagnosis and treatment.So it is of significance to the early diagnosis of colorectal cancer.Invasion and metastasis are two important features in tumors.MMPs(Matrix metalloproteinases),capable of degrading extracellular matrix(ECM),pave the way for the invasion and distant metastasis of tumor cells.Type IV collagen is an important component of both ECM and basement membrane(BM).MMP-9(Matrix metalloproteinase-9),with the most biggest molecular weight in MMPs,can degrade the component of type IV collagen etc.,which contributes to the invasion and metastasis of tumors.TIMP-1(Tissue inhibitor of metalloproteinase-1)can combine with MMP-9 in the proportion of 1:1,inhibiting the proteolytic activity of MMP-9.MMP-9 and TIMP-1 both had been studied as biomarkers,but not been implied in the clinical practice until now.On the one hand,the relationship between these two markers and the clinical pathological features still remained controversial;on the other hand,the expression and mechanism of MMP-9 and TIMP-1 in tumors still remained unclarified.Purpose:The aim of this study was to investigate the expressions of MMP-9 and TIMP-1in the tissue and serum of patients with colorectal cancer respectively and analyze their relationship with clinical pathological characteristics and make it clear if both of them can be used as biomarkers or not,which will provide help for diagnosis and treatment of colorectal cancer.Methods:(1)44 cases of colorectal cancer tissue and their adjacent normal tissue were selected who underwent surgical removal at the Second Hospital of Jilin University between March 2015 and March 2016.The expressions of MMP-9 and TIMP-1 in the tissue were detected by immunohistochemistry and Western blot.Their relationship with clinical pathological characteristics was analyzed.The data were statistically analyzed by SPSS20.0 software.(2)73 colorectal cancer patients,24 colorectal adenoma patients and 24 healthy subjects were selected,the first two groups of which were underwent surgical removal at the Sino-Japanese Friendship Hospital of Jilin University between September 2014 and September 2015.Serum MMP-9 and TIMP-1 were measured using ELISA,while serum CEA and CA19-9 were detected by electrochemiluminescence method.The relationship between the obtained results and clinical pathological characteristics was investigated.ROC curve was used to assess the diagnostic value of those four markers in serum.Log Rank test was used to analyse date of the survival rate of patients with the survival curve,and compare their prognostic value.The data were statistically analyzed by SPSS20.0 software.Results:(1)MMP-9 and TIMP-1 were higher in colorectal cancer than its corresponding normal tissue.MMP-9 was not related with TIMP-1 in colorectal cancer.MMP-9 and TIMP-1 in colorectal cancer did not correlate with age,sex,pathologic type,size,and site(p>0.05),but not correlated with histological differentiation and stage(p<0.05).For patients with colorectal cancer,the positive rate of MMP-9 and TIMP-1 in poorly differentiated were higher than those in well and moderately differentiated.MMP-9 and TIMP-1 in III/VI stage were higher than those in I/II stage.(2)There was significance(p < 0.05)among colorectal cancer group,colorectal adenoma group and healthy subjects group as to serum MMP-9、TIMP-1、CEA and CA19-9,which decreased with groups.All of them did not correlate with age,sex,site(p>0.05),but correlated with tumor diameter,distant metastasis,survival or not,Duke stage,degree of bowel wall invasion,lymph nodes involved in,differentiation(p<0.05).The results of ROC showed that area under curve(AUC)of serum MMP-9、TIMP-1、CEA and CA19-9 between colorectal cancer patients and healthy subjects were 0.768、0.854、0.663 and 0.616 respectively in return.The survival rate of patients of high serum levels of MMP-9 and TIMP-1 was lower than that of in patients with low serum levels of them.But survival rate between patients with high and low serum CEA and CA19-9 had no difference.Conclusions:(1)We demonstrated that MMP-9 and TIMP-1 in colorectal cancer tissue were higher in normal tissue,moreover,MMP-9 and TIMP-1 in colorectal cancer tissue correlated with stage and degree of differentiation,suggesting that MMP-9 and TIMP-1 may involve in the invasion and metastasis of colorectal cancer.(2)We demonstrated that,among colorectal cancer group,colorectal adenoma group and healthy subjects group,serum MMP-9 、 TIMP-1 、 CEA and CA19-9decreased with groups,serum MMP-9、TIMP-1、CEA and CA19-9 correlated with tumor diameter,distant metastasis,survival or not,Duke,s stage,degree of bowel wall invasion,lymph nodes involved in,differentiation,indicating that four biomarkers may involve in the invasion and metastasis of colorectal cancer in our study.(3)Our study suggested that serum MMP-9、TIMP-1 had certein diagnosis and prognostic value for colorectal cancer.