Expression And Clinical Significance Of CCL5 In Gastric Cancer

Background:The invasion and metastasis of cancer is the main cause leading to gastric cancer patients' death.To study the mechanism and molecule related to the invasion and metastasis of gastric cancer can provide new ideas for the development of treatment and prognosis of patients.Tumor associated macrophages(TAM)is an important kind of inflammatory cell in the tumor interstitial.They are formed by blood circulating monocytes recruited to tumor interstitial through a variety of factors,including chemokines.TAM can promote tumor's growth,invasion and metastasis by secreting a variety of cytokines.Chemokines,which play an important role in the inflammatory response,are a class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes.In recent years,more and more studies have shown that chemokines play an important role in tumor's growth,invasion and metastasis.C-C motif chemokine ligand 5(CCL5)is a member of the CC chemokine family and is considered to be a biological indicator of potential for tumor diagnosis and prognosis evaluation.A variety of studies have found that the relationship between high expression of CCL5 and the biological behaviors of many kinds of tumor is close.Studies have also shown that by blocking the CCL5 / CCR5 axis,the development of tumor can be inhibited.At present,there are few reports about the relationship between expression of CCL5 in gastric cancer and its biological behavior,as well as the prognosis of patients.Objective:To investigate the expression of CCL5 and TAM marker CD68 in gastric cancer tissues,adjacent tissues and normal gastric tissues,and to explore the relationship between CCL5 and clinical pathological features of gastric cancer,TAM level in gastric cancer and the prognosis of gastric cancer.Materials:61 patients who performed radical gastrectomy for gastric cancer at the Qingdao Municipal Hospital from January 1,2010 to May 30,2013 were enrolled in this study.Collect the clinical data,pathologic data and follow-up data.Another 20 healthy people were selected as the control group.All of them were confirmed to benegative by endoscopic pathology.The specimens were taken from endoscopic biopsy tissues.The pathological paraffin blocks are collected in pathology department of Qingdao Municipal Hospital.Methods:SP immunohistochemical method was used to detect CCL5 and CD68 in gastric cancer tissues,adjacent tissues and normal gastric tissues.Using SPSS 20.0software for statistical analysis,using ?~2 test to analyze the correlation between the CCL5 in gastric cancer tissues,adjacent tissues and normal gastric tissues,and the correlation between expression of CCL5 and clinical pathological features of gastric cancer.Spearman rank correlation analysis was used to determine the relationship between the expression of CCL5 and TAM level,and the survival curve was determined by Kaplan-Meier method,using Log-rank to analyze the correlation between the expression of CCL5 and the prognosis of patients.Results:CCL5 was mainly expressed in the cell membrane and cytoplasm.The expression of CCL5 in gastric cancer tissues was higher than that of normal gastric tissue and adjacent tissues(?~2=34.321,P<0.001;?~2=20.758,P<0.001).Correlation analysis showed that high level expression of CCL5 in gastric cancer was significantly correlated with advanced TNM stage(?~2=0.229,P=0.632),invasion depth(?~2=8.050,P=0.005),lymphnode metastasis(?~2=12.108,P<0.001),tumor thrombus(?~2=4.921,P=0.027),but not correlated with gender(?~2=0.229,P=0.632),age(?~2=1.313,P=0.252)and the degree of tumor differentiation(?~2=0.006,P=0.939).The expression of CCL5 is positively corrected with the degree of TAM(r=0.449,P<0.001).The 3 year cumulative survival rates of patients with low CCL5 expression was71%(22/31),the 3 year cumulative survival rates of patients with high CCL5 expression was 46.7%.Patients with a lower CCL5 expression had a significantly longer overall survival(?~2=4.575,P<0.05).Conclusions: CCL5 may be associated with the invasion and metastasis of gastric cancer and the prognosis of patients.The mechanism may be related with the functions of TAM.CCL5 can be used as a marker to appraise patient's prognosis,may become a potential therapeutic target for gastric cancer intervention.