Expression And Clinical Significance Of CD47 And SIRP? In Esophageal Squamous Cell Carcinomas

BackgroundEsophageal cancer(EC)is one of the common causes of cancer-related deaths in the world.In China,there are about 500000 new patients with esophageal cancer every year.At present,the standard treatment of EC is surgery or surgery combined with radiotherapy and chemotherapy.However,the 5-year survival rate of patients with advanced esophageal cancer is still very low.In recent years,the immune checkpoint inhibitor represented by PD-1/PD-L1 antibody has shown its effect on a variety of malignant tumors,and its effectiveness in esophageal cancer has been confirmed.However,some studies have shown that the use of PD-1/PD-L1 antibody alone is not enough to cause tumor regression in most cancer patients,so it is necessary to find new immunotherapeutic targets.In recent years,the role of CD47-SIRP? signal axis in tumor immunotherapy has attracted much attention.CD47(cluster of differentiation 47)is a transmembrane protein,which is widely expressed on the surface of normal cells.Many previous studies have shown that it is highly expressed on the surface of a variety of tumor cells.SIRP?(signal regulatory protein alpha)is widely expressed in many tissues.It plays an important role as an important ligand of CD47 when it is expressed in myeloid cell membranes such as macrophages,dendritic cells,granulocytes and monocytes,.The combination of the two makes tumor cells resistant to host immune surveillance,which is one of the mechanisms of immune escape.Therefore,blocking the interaction between CD47 and SIRP? may be a new strategy for the treatment of esophageal cancer.Many studies have confirmed that CD47 is highly expressed on the surface of many kinds of tumor cells,and its expression is related to poor prognosis,but the mechanism of SIRP? in tumor is not clear.Some studies have confirmed that the expression of SIRP? is down-regulated in breast cancer,liver cancer,prostate cancer and so on.However,it has also been reported that SIRP? is more significantly expressed in renal cell carcinoma and melanoma than surrounding normal tissues,while the expression of SIRP? in esophageal squamous cell carcinoma(ESCC)is not clear.At present,there are few studies on the role of CD47 in ESCC,and most studies have confirmed that CD47 is highly expressed in ESCC,but the results on the relationship between CD47 and clinicopathological characteristics,prognosis of ESCC are not consistent.The purpose of this study was to detect the expression of CD47 and SIRP? in ESCC,and to explore the relationship between them and the clinicopathological features and prognosis of ESCC.PurposeTo investigate the expression of CD47 and SIRP? protein in esophageal squamous cell carcinoma,to analyze their relationship with the clinicopathological features of esophageal squamous cell carcinoma,and to explore the relationship between them and the prognosis of esophageal squamous cell carcinoma.Methods1.We collected the clinical and pathological data of the patients with esophageal cancer who underwent surgical treatment at the Affiliated Tumor Hospital of Zhengzhou University from January 2012 to December 2013,the wax specimens of cancer tissues and corresponding paracancerous tissues.2.We used immunohistochemical SP method to detect the expression levels of CD47 and SIRP? in tumor tissues and paracancerous tissues.3.Analytical methods: The ?2 test was used to analyze the relationship between the expression of CD47 and SIRP? and the clinicopathological features of ESCC.The correlation between the expression of the two proteins was analyzed by Pearson test.Use the Kaplan-Meier method for survival analysis.Cox risk model was used to analyze the expression of the above proteins,the relationship between the related clinicopathological features and the prognosis of ESCC.Results1.Both CD47 and SIRP? are expressed in esophageal cancer cell cytoplasm and cell membrane.2.In 65 cases of esophageal cancer,the positive expression rate of CD47 was 66.2%,the positive expression rate of paracancerous tissues was 27.7%.The expression of CD47 in esophageal cancer tissues was significantly higher than that adjacent tissues,and the difference was statistically significant(P<0.05);The positive expression rate of SIRP?was 36.9%,and the positive expression rate of adjacent tissues was 56.9%.The expression of SIRP? in esophageal cancer tissues was lower than that in paracancerous tissues,the difference was statistically significant(P=0.022).3.The expression of CD47 was associated with tumor invasion depth(P=0.002),lymph node metastasis(P=0.01),TNM stage(P=0.015),histological grade(P=0.002),gender(P=0.065),age(P=0.065),tumor site(P=0.542),pathological type(P=0.647)were unrelated;SIRP?expression was associated with histological grade(P=0.017),gender(P=0.916),age(P=0.818)Tumor site(P=0.986),depth of invasion(P=0.350),lymph node metastasis(P=0.131),TNM stage(P=0.486),pathological type(P=0.612)were not relevant.4.The 5-year survival rates of the CD47-positive group was 16.1% and the negative group was 48.3%,the difference was statistically significant(P=0.001).The 5-year survival rate of the SIRP?-positive group was 33.3% and the 5-year survival rate of the negative group was 23.6%.There was no difference between the two(P=0.183).5.Univariate analysis of Cox risk model showed that depth of invasion(P=0.030),lymph node metastasis(P=0.020),histological grade(P=0.043),and CD47 expression(P=0.003)were correlated with OS,and multivariate analysis suggested lymph node metastasis(HR 2.654,95% confidence interval 0.876-4.153,P=0.043),CD47(HR 2.099,95% confidence interval 0.983-5.063,P=0.050)were independent prognostic factors for OS in ESCC patients.6.Pearson correlation test showed that there was a negative correlation between the expression of CD47 and the expression of SIRP? in 65 patients with ESCC(R=-0.261,P=0.036).Conclusions1.CD47 is highly expressed in esophageal squamous cell carcinoma,and the SIRP? was lowly expressed in esophageal squamous cell carcinoma.2.CD47 is an independent risk factor for the poor prognosis of patients with esophageal cancer.3.There was a negative correlation between the expression of CD47 and the expression of SIRP?.