Expression And Significance Of CD276,CD133 Combined With CEA And CA199 In Colorectal Cancer And Its Precancerous Diseases

Background and ObiectivesThe incidence of colorectal cancer(CRC)has gradually risen in recent years and has become the world’s No.3 malignant tumor that endanger humans’ life and health.Due to the lack of specificity,low sensitivity and the limited value of evaluating the CRC of the commonly used CRC tumor markers such as Carcinoembryonic antigen(CEA)and carbohydrate antigen 19-9(CA19-9)and the hoddenly early clinical symptoms,it was mostly in the middle and late stages when CRC was diagnosised.So the 5-year survival rate also decreased,only 40-50%.Therefore,it has become a major direction of CRC research to finding a new marker or combined CEA,CA199 detection to increase the detection rate of CRC.It was observed that the immunomodulatory factor CD276 and tumor stem cell marker CD133 can be overexpressed in the CRC and associated with CRC invasion,metastasis,chemoresistance,tumor recurrence and shortened survival.The overexpression of CD276 and CD133 induces anti-apoptosis,migration and invasion through the JAK2/STAT3 signaling pathway in colorectal cancer,and in turn,increased the expression of the downstream anti-apoptotic proteins Bcl-2,Bcl-x,MMP9.Colorectal polyps are the precancerous diseases of CRC.There is no study on CD276 and CD133 in colorectal polyp.The goal of the present study was to explore the value of CD276 and CD133 or combining with CEA and CA199 in predicting the occurrence,development and prognosis of CRC by testing the expression of CD276,CD133 and the serum levels of CEA and CA19-9 in CRC and colorectal polyps.Materials and MethodsNinety-four cases of CRC,28 cases of high-grade adenoma,31 cases of low-grade adenoma,22 cases of non-adenomatous polyps and 10 cases of normal intestinal mucosa specimens of surgical or biopsy were retrospective analysis in the Second Affiliated Hospital of Zhengzhou University from October 2012 to April 2017.Immunohistochemical methods was used to detect CD276,CD133 expression in the specimen.The values of serum CEA,CA199 were collected in all the patients.Ninety-four cases of CRC patients were followed up.SPSS 22.0 and SAS software were used for statistical analysis.Results1.There were 56 cases of CD276,59 cases of CD133,46 cases of CEA and 33 cases of CA19-9 postively expression in 94 cases of CRC,respectively.All of them were related to the lymph node metastasis,distant metastasis and short survival of CRC.The difference was statistically significant(P<0.05).2.There were 40 cases of CD276 and CD133,29 cases of CD276 and CEA,22 cases of CD276 and CA19-9,28 cases of CD133 and CEA,19 cases of CD133 and CA19-9,and 29 cases of CEA and CA19-9 postively coexpression.The positive coexpression in each group was associated with the occurrence of CRC,lymph node metastasis and distant metastasis compared with the single or all negative expression(P<0.05).The overall survival of double positives in each group was shorter than that in single positive or negative ones.3.CD276 was not expressed in normal mucosa and non-adenomatous polyps,but only in adenomatous polyps and CRC.The expression of CD276 in high-grade adenoma group was significantly higher than that in low-grade adenoma group(P <0.05),but not between CRC and high-grade adenoma group.CD133 was low expressed in non-adenomatous polyps.The expression of and CD133 in high-grade adenomas was significantly higher than the low-grade adenomas group(P<0.05).The values of serum CEA and CA199 were obviously higher in CRC than the other groups.The difference was statistically significant(P<0.05).4.CD276,CD133,CEA and CA199 positive and double positive expression group showed a gradual increase in the positive rate of CRC expression from normal intestinal mucosa,non-adenomatous polyps,low-grade adenomas,high-grade adenomas to CRC(P<0.05).The positive rates of double positive expression of CD276/CEA,CD133/CEA and CEA/CA199 in CRC group were significantly higher than those in high grade adenoma group.The positive rates of CD276/CD133 and CD133/CA199 in both groups were significantly higher than those in low grade adenoma group(P<0.05).Conclusions1.Immunoregulatory factors CD276,tumor stem cell markers CD133,CEA and CA199 play a role in the development of CRC,and are associated with poor prognosis such as lymph node metastasis,distant metastasis and shortened survival of CRC.2.CEA and CD276,CD133,CA199 dual-positive highly predictive of the possibility of CRC,CD276 and CD133 may become the early diagnostic tumor markers of CRC.3.The detection indexes of CD276,CD133,CEA and CA199 play a role in the progression of colorectal polyps to CRC.Suggesting that CD276 and CD133 may beome the markers to prediction the invasive carcinoma in adenomas.