Correlation Between Tumor Associated Macrophages And Epithelialmesenchymal Transition In Colorectal Cancer

Background:Colorectal cancer(CRC)is a malignant tumor with high morbidity and mortality in our country.Most patients with CRC have metastasized at a distance,and the most common site of metastasis is liver metastasis.Tumor-associated macrophages(TAMs)are a kind of immune cells that infiltrate the tumor microenvironment.In recent years,TAMs as a new immunotherapy target,have become a research hotspot in the field of tumor immunotherapy.However,the role of TAMs in CRC metastasis is still controversial,and the relationship between TAMs and epithelial-mesenchymal transition(EMT)is still unclear,and further research is needed.Objective:This project aims to study the expression of TAMs in CRC tissues,to clarify the relationship between TAMs and CRC clinicopathological characteristics,and to further analyze the correlation between TAMs and EMT,and to preliminarily explore the molecular mechanism of EMT in CRC,as a treatment for CRC patients Looking for new therapeutic targets and theoretical basis.Methods:A retrospective analysis of the clinicopathological data of 58 CRC patients who were admitted to the general surgery department of our hospital from September 2016 to November 2018.Use electronic medical record retrieval to record the patient’s age,gender,preoperative CEA,tumor diameter,TNM stage,presence or absence of lymph node metastasis,tumor location,tumor histological type,mismatch repair protein(MLH1,MSH6,PMS2,MSH2),and more Drug resistance-related proteins(TS,Pgp,GST-π,ERCC1,LRP),and telephone follow-up;collect surgically resected CRC tissue,part of paired adjacent tissues and liver metastasis tissue specimens,and use immunohistochemical methods to detect these specimens The expression of TAMs markers(CD68,CD163)and EMT markers(E-cadherin,Vimentin).The SPSS25.0statistical software was used to analyze the data.The pairwise comparison of the expressions of CD68,CD163,E-cadherin,and Vimentin in CRC tissue and its paired adjacent tumor and liver metastatic cancer tissues used two-sided t test;The correlation of CD68,CD163 and E-cadherin,Vimentin expression in CRC tissues was analyzed by Spearman rank correlation analysis;the correlation between the expression of CD68,CD163,E-cadherin,and Vimentin in tissues and the clinical and pathological data of CRC patients was tested by chi-square test;Kaplan-Meier method was used for survival analysis and the survival curve was drawn.In all cases,a P value of<0.05 was considered statistically significant.Results:CD68 and CD163 are mainly located in the interstitium of CRC tissue,and are more common around the tumor necrosis area.The expression score of CD68 and CD163 in CRC tissue is significantly higher than that of paired adjacent tissues,and the difference is statistically significant(t=5.722,t=6.571,P<0.05);and compared with liver metastasis tissues,the expression scores of CD68 and CD163 in primary CRC tissues and liver metastasis tissues were not significantly different(t=0.566,P=0.557;t=1.288,P=0.215).The expression score of E-cadherin in paired adjacent tissues was significantly higher than that of cancer tissues(t=-3.907,P<0.05),and the expression score of Vimentin in cancer tissues was significantly higher than that of paired adjacent tissues(t=3.652,P<0.05),The difference is statistically significant.Analysis of the correlation between CD68,CD163 and E-cadherin and Vimentin in CRC organization shows that there is a negative correlation between CD68 and Vimentin(r_s=-0.375,P=0.004),while CD163 is not seen with E-cadherin and Vimentin Correlation.The correlation analysis of CD68,CD163,E-cadherin,Vimentin and the clinicopathological characteristics of CRC patients showed that the high expression of CD68 was positively correlated with TNM staging(χ~2=6.623,P<0.05),and negatively correlated with lymph node metastasis(χ~2=4.351,P<0.05),negatively correlated with liver metastasis(χ~2=5.994,P<0.05),but not related to other clinicopathological characteristics(P>0.05);CD163 high expression was positively correlated with lymph node metastasis(χ~2=7.707,P<0.05),positively correlated with liver metastasis(χ~2=5.393,P<0.05),but not correlated with other clinicopathological characteristics(P>0.05);E-cadherin expression was negatively correlated with lymph node metastasis(χ~2=8.438,P<0.05),positively correlated with TNM staging(χ~2=4.634,P<0.05),but not related to other clinicopathological characteristics(P>0.05);Vimentin expression was positively correlated with lymph node metastasis(χ~2=11.231,P<0.05),It was positively correlated with liver metastasis(χ~2=4.700,P<0.05),positively correlated with TNM staging(χ~2=4.006,P<0.05),and not related to other clinicopathological characteristics(P>0.05).Analyzing the correlation between CD163,CD68 and the prognosis of CRC patients,it was found that the overall survival and disease-free survival of patients in the high expression group and low expression group of CD163 and CD68 were not significantly different(P>0.05).Conclusion:1.In CRC,the expression of E-cadherin is decreased,and the expression of Vimentin is increased,which promotes the invasion and metastasis of CRC.2.The expression of CD68 TAMs in CRC is significantly higher than that in adjacent tissues,and is negatively correlated with lymph node metastasis,and negatively correlated with the expression of Vimentin,and has the effect of inhibiting the occurrence of EMT and tumor progression in CRC.3.The expression of CD163TAMs in CRC is higher than that in adjacent tissues,and is positively correlated with lymph node metastasis and liver metastasis in patients with CRC,and promotes the progression and metastasis of CRC.