The Expression Of CD163 And MIF In Non-small Cell Lung Cancer And Its Effect On Angiogenesis

BackgroundLung cancer is the leading cause of death from cancer worldwide,and approximately 80%of lung cancers are non-small cell lung cancer(NSCLC).The incidence of NSCLC is increasing annually because of growing smoking rates and environmental pollution.Despite advances in treatment,its prognosis is still poor and the 5-year relative survival rate is only about 15%.Therefore,the identifcation of molecular mechanisms underlying its metastasis and progression can improve the effects of lung cancer therapies.A tumor is a heterogeneous mass of malignant cells that co-exists with nonmalignant cells,and the presence of non-malignant cells provides a protumorigenic niche known as the tumor microenvironment(TME).TME assists tumor outgrowth by secreting growth factors,anti-apoptotic factors,and maintaining animmunosuppressiveenvironment.Macrophageswithinthetumour microenvironment termed tumour associated macrophages(TAMs),the presence of TAMs has been connected with the invasion,angiogenesis,hypoxia and early occurrence of metastasis.Based on their function,TAMs are divided broadly into two subtypes:M1 classically-activated macrophages and M2 alternatively-activated macrophages.The M1 macrophage is involved in the inflammatory response,pathogen clearance,and antitumor immunity.In contrast,the M2 macrophage downregulate inflammatory response,participate in wound healing,and pro-tumorigenic properties,which is critical modulators of the tumor microenvironment.In the early or regression stages of tumors,TAMs adopt the M1-like phenotype for the inhibition of angiogenesis in conjunction with the activation of tumor immunity.In contrast,TAMs shift to a M2-like state to enhance tumor angiogenesis in advanced tumors.Mcrophage migration inhibitory factor(MIF)is a pluripotent and pleiotropic protein cytokine and it is constitutively expressed in a variety of immune and non-immune cells.Experimental and clinical studies show that high levels of MIF are found in almost all types of human cancers and are implicated in seemingly all stages of development of the tumors.MIF readily contributes to a microenvironment favoring tumor growth and prolif-eration by promoting angiogenesis.ObjectiveTo study the expression differences of M2 TAMs and related factors MIF in non-small cell lung cancer tissues and adjacent tissues,analyze their relationship with clinicopathological features of non-small cell lung cancer patients,and further explore the effect of expression of M2 TAMs and MIF on tumor angiogenesis.MethodsThe NSCLC specimens that were excised from the Department of Thoracic Surgery of the First Affiliated Hospital of Zhengzhou University between December2012 and December 2014 were collected.Finally,84 patients were enrolled and their gender,age,histopathological type,and lymph node metastasis were obtained through the in-hospital e-health system and were revised.According to the International Association For The Study Of Lung Cancer(IASLC),The eighth edition of the lung cancer staging standard performs TNM staging.In addition,30 patients with NSCLC were randomly selected as the control group.Paraffin-embedded tissues of all lung cancer tissues were fixed with 4%formaldehyde,paraffin-embedded and confirmed by hematoxylin-eosin staining.Immunohistochemistry was used to detect the expression of M2 TAMs(marked by CD163),MIF,and tumor microvessel density(marked by CD34)in the tissues.All data were statistically analyzed using SPSS21.0 statistical software.The mean and standard deviation((?)±s)was used to describe the data and the t-test was used to compare the data between the two groups.The two separate groups of two groups were tested by the chi 2 test.Spearman rank correlation analysis was used.The test level is 0.05.Results1 CD163-positive cells showed tan or brown particles in the cytoplasm;CD163counts in NSCLC tissues were higher than those in adjacent tissues,and there was a statistically significant difference between them(t=8.630,P<0.05).The MIF positive signal was brownish-yellow granular,and the expression was mainly located in the cytoplasm and nucleus,and a few in the nucleus.The expression of MIF in NSCLC tissues was higher than that in the paracancerous tissues.The difference between the two was statistically significant(?~2=30.982,P<0.05).2 There was no significant difference in the expression of CD163 and MIF between patients with NSCLC and gender,age,pathological type,and lymph node metastasis(P>0.05).When the CD163 expression was high,the TNM staging was later,and the difference was statistically significant(?~2=4.731,P<0.05).When the MIF was highly expressed,the TNM staging was later,and the difference was statistically significant(?~2=4.270,P<0.05).3 When CD163 was highly expressed in NSCLC tissues,the count of CD34increased,and the difference was statistically significant(t=8.333,P<0.05).When the MIF was highly expressed,the count of CD34 increased,and the difference was statistically significant(t=6.417,P<0.05).4 There was a positive correlation between CD163 and MIF expression(rs=0.392,P<0.05).Conclusions1 The M2 TAMs and their related factors MIF are closely related to TNM staging in NSCLC tissues,and its mechanism may be achieved by promoting tumor angiogenesis.2 The role of M2 TAMs in the development of NSCLC may be related to MIF.