The Clinical Significance Of CD59 Expression On Pancreatic Cancer Tissue And The Relationship Between CD59 Expression And Tumor-associated Macrophage Infiltration

ObjectivePancreatic ductal adenocarcinoma(PDAC)is a common type of devastating diseases in digestive system with high malignant degree and mortality.About 80%patients lost the opportunity for operation because of the difficulty of early diagnosis of PDAC.Despite significant advances in the diagnosis and treatment of PDAC,the prognosis of pancreatic cancer remains dismal.Overall,less than 6-7%of individuals will survive 5 years beyond their diagnosis.The formation of tumor is the result of the interaction between cancer cells and a variety of cells in the matrix.Tumor-associated macrophages(TAM)play a critical role in the process.CD59,one of membrane complement regulatory proteins(mCRPs),is a GPI-anchored membrane protein that regulates complement activation by inhibiting the formation of the membrane attack complex(MAC).The high expressed CD59 on cancer cells,such as pancreatic cancer,lung cancer,breast cancer,colorectal cancer,prostatic cancer,lymphoma,leukemia,can not only inhibit the function of complement,but also protect cells from apoptosis cascade reactions directly by several signal pathways.CD59 can also cause the influence of immune activities on immune cells,such as T cells,NK cells,B cells and DC cells.However,the roles of CD59 in the tumor microenvironment is still not been detailed,especially the function of CD59 on TAM.In the recent studies,the distribution of mouse homolog of human CD59(Ly6c)is consistent with the M2 type macrophages(TAM)in the tumor-burdened mice model.In bone marrow-derived macrophages,the expression of CD59 varies in different types.However,whether CD59 influences the differentiation of macrophages is not clear and the function of CD59 in human macrophages,especially TAM,have been seldom reported.It is the focus of this project.Based on the interaction between pancreatic cancer cells and macrophages in the tumor microenvironment,we suppose to explore the distribution of TAM in PDAC tissues and the relationship between the distribution and the clinical characteristics and prognosis of PDAC patients.Then we explore whether it could improve the anti-tumor effect of gemcitabine through the intervention of CD59 expression on TAM to provide a new method for the comprehensive treatment of PDAC.Methods:1.The level of CD59 expression was evaluated by tissue microarray-based immunohistochemistry on cancer and adjacent-cancer tissues from 85 PDAC patients.We analyzed he relationship between the levels of CD59 and the clinical characteristics and the overall survival of these patients.2.Based on the analysis of CD59 expression on pancreatic tissues,we also analyzed the relationship between the tumor associated macrophage infiltration in pancreatic tissue and the prognosis of PDAC patients,and the relationship between CD59 expression and the tumor associated macrophage infiltration in pancreatic cancer tissues.Results:1.The expression of CD59 in the PDAC tissue was higher than the expression in the adjacent tissues(p=0.027).The expression level of CD59 was associated with the gender(p=0.008)and the pathologic grading of cancer tissue(p=0.002).The expression of CD59 was related to the overall survival of patients(p=0.037).Multivariable analysis found that CD59 expression was not the independent risk factors affecting the prognosis of PDAC patients.But survival analysis of different subgroups showed that CD59 was the independent risk factors affecting the prognosis of patients younger than 60 years old(p=0.015).2.The prognosis of PDAC patients was associated with the tumor associated macrophage infiltration(p=0.047).The expression level of CD59 was associated with TAM infiltration(p<0.001).Conclusion:1.The expression of CD59 was higher in the cancer tissue and it was related to the poor prognosis of PDAC patients.The expression of CD59 was related to the overall survival of patients.But CD59 expression was not independent risk factors affecting the prognosis of PDAC patients.However,CD59 was the independent risk factors of patients younger than 60 years old.2.The level of tumor associated macrophage infiltration was related to the overall survival of patients.The prognosis of PDAC patients and the expression level of CD59 were associated with the tumor associated macrophage infiltration.