The Relationship Between Expression Of ICAM-3 And LFA-1 And Invasion And Metastasis Of Esophageal Squamous Cell Carcinoma

Esophageal cancer is the most common digestive tract cancer.About 572,000 people worldwide are newly diagnosed with esophageal cancer every year.About 590,000 people die of esophageal cancer,ranking seventh and sixth among all tumors,respectively.At the same time,there are obvious regional differences among patients with esophageal cancer,especially in East Asia,where the high incidence of esophageal cancer is in the central and eastern regions of China.Nowadays,esophageal cancer has become the fifth most common and fourth deadly cancer in Chinese men.According to pathological types,esophageal cancer can be divided into squamous cell carcinoma and adenocarcinoma.In China,about 90% of esophageal cancer is squamous cell carcinoma.Squamous cell carcinoma often occurs in upper and middle esophagus.Smoking and drinking are the most important risk factors for esophageal squamous cell carcinoma.Esophageal adenocarcinoma,obesity,gastric reflux disease and Barrett esophagus are the most common causes of esophageal adenocarcinoma.In addition to the above factors,the incidence of esophageal cancer is also related to genetic factors and environmental factors,but the specific etiology is still unclear.Since 1950 s,the research of molecular biology has developed rapidly.The discovery of oncogenes and anti-oncogenes is a major breakthrough in molecular biology.The pathogenesis of tumors is gradually approaching the genetic theory.The exfoliation of anti-oncogenes and the amplification of oncogenes caused by various internal and external factors may be the fundamental causes of cancer.The occurrence and development of cancer and the angiogenesis of tumors are fine.Cell differentiation,cell apoptosis and signal transduction between cells are closely related.The proliferation and metastasis of cancer cells are mainly the result of adhesion molecules and extracellular matrix on the surface of cancer cells and the interaction between cells and cells.Intercellular adhesion molecule-3,also known as CD50,is a member of the immunoglobulin superfamily of adhesion molecules.They are expressed on the cell surface in the form of receptors or ligands,mediate cell-extracellular matrix and cell-to-cell adhesion,and play an important role in the metastasis of cancer cells,angiogenesis and proliferation of vascular endothelial cells.LFA-1 is a heterodimer protein of integrin family,which is expressed on almost all white blood cells.Recently,LFA-1 has been reported in several solid tumors,including colorectal cancer.LFA-1 has two subunits,alpha and beta,and ICAM binding sites are located in alpha subunit.In the inactivated state,LFA-1 exhibits a bending conformation with a low affinity for ICAM,which hides MIDAS.When chemokines stimulate type I domains on beta subunits,this results in the binding of MIDAS sites on beta subunits to glutamic acid in type I domains of alpha subunits.This binding process causes beta subunits to pull down the alpha 7 helix of the I domain,expose and open Midas sites on alpha subunits,which results in conformational changes of LFA-1 and the formation of fully stretched conformation,thus binding with ICAM-3.Combine.In the invasion and metastasis of esophageal squamous cell carcinoma,the abnormal activation of LFA-1 may promote the occurrence and development of esophageal squamous cell carcinoma by regulating the expression of ICAM-3.ICAM-3 and LFA-1 play an important regulatory role in the occurrence and development of esophageal squamous cell carcinoma,but they are rarely reported in the invasion and metastasis of esophageal squamous cell carcinoma.In order to investigate the relationship between the expression of ICAM-3 and LFA-1 and invasion and metastasis of esophageal squamous cell carcinoma,the expression of ICAM-3 and LFA-1 in esophageal squamous cell carcinoma and normal esophageal mucosa were detected by immunohistochemistry and in situ hybridization,and the relationship between the expression of ICAM-3 and LFA-1 in the occurrence,invasion and metastasis of esophageal squamous cell carcinoma was discussed.Material and method1.Esophageal squamous cell carcinoma tissue specimens: From September 2015 to May 2017,53 specimens of esophageal squamous cell carcinoma and 26 specimens of normal esophageal mucosa from the First Affiliated Hospital of Zhengzhou University and Henan People’s Hospital were selected as control group.No preoperative radiotherapy or chemotherapy was given to the patients.2.The expression of ICAM-3 and LFA-1 protein in 53 cases of esophageal squamous cell carcinoma and 26 cases of normal esophageal mucosa were detected by immunohistochemical SP method.3.The expressions of ICAM-3 and LFA-1 in 53 cases of esophageal squamous cell carcinoma and 26 cases of normal esophageal mucosa were detected by in situ hybridization.4.Statistical processing: The above data were analyzed and counted by SPSS 10.0 software.2 test was used to compare the positive rates and Spearman correlation analysis was used to analyze the variables,and the test level a = 0.05.Result 1.The positive expression rates of ICAM-3 protein and ICAM-3 mRNA in esophageal squamous cell carcinoma were 69.8% and 64.2%,respectively,which were significantly higher than those in normal esophageal mucosa(3.8% and 3.8%,P < 0.05).2.The positive expression rates of ICAM-3 protein and ICAM-3 gene in the whole layer group were 81.8% and 75.8% respectively,which were significantly higher than those in the deep layer group(60.0%,53.3%)and the superficial layer group(20%,20%).The expression rates of ICAM-3 protein and mRNA were significantly different among the three groups(P < 0.05).3.With the increase of histological grade,the positive rates of ICAM-3 protein expression were 100%,70.8% and 43.8% respectively,and the positive rates of ICAM-3 mRNA expression were 100%,70.8% and 25% respectively.There was a significant difference between the two groups(P < 0.05).4.The positive expression rates of ICAM-3 protein and ICAM-3 gene in esophageal squamous cell carcinoma without lymph node metastasis were 51.9% and 48.1% respectively,which were significantly lower than those in lymph node metastasis group(88.5% and 80.8%,respectively).There was statistical significance between the two groups(P < 0.05).5.The positive expression rates of LFA-1 protein and LFA-1 gene in esophageal squamous cell carcinoma tissues were 73.6% and 69.8%,respectively,which were significantly higher than those in normal esophageal mucosa tissues(26.9% and 3.8%,P < 0.05).6.The positive expression rates of LFA-1 protein and mRNA were 81.8% and 81.8% in the whole layer group,which were significantly higher than 73.3%,60%.in the deep layer group and 20% and 20% in the superficial layer group.There was a significant difference in the expression rates of LFA-1 protein and mRNA between the three groups(P < 0.05).7.With the increase of histological grade,the positive rates of LFA-1 protein expression were 100%,79.2% and 43.8% respectively,and the positive rates of LFA-1 gene expression were 100%,87.5% and 18.8% respectively.The difference between the two groups was significant,P < 0.05,with statistical significance.8.The positive expression rates of LFA-1 protein and LFA-1 gene in esophageal squamous cell carcinoma without lymph node metastasis were 59.2% and 55.6% respectively,which were significantly lower than those in lymph node metastasis group(88.5% and 84.6%,respectively),P < 0.05.9.The expression of ICAM-3 and LFA-1 protein and mRNA in esophageal squamous cell carcinoma tissues were correlated with each other.There was a positive correlation between ICAM-3 and LFA-1 protein and mRNA levels.(r=0.390,r=0.509,P<0.05).Conclusion 1.The expression of ICAM-3 and LFA-1 in esophageal squamous cell carcinoma was increased,which indicated that the high expression of ICAM-3 and LFA-1 was related to the occurrence of esophageal squamous cell carcinoma.2.The expression of ICAM-3 and LFA-1 protein and mRNA increased in lymph node metastasis group,deep infiltration group and poorly differentiated group,suggesting that the high expression of ICAM-3 and LFA-1 is related to the degree of invasion,metastasis and differentiation of esophageal squamous cell carcinoma.3.The expression of ICAM-3 and LFA-1 protein and mRNA was positively correlated in esophageal squamous cell carcinoma,suggesting that the abnormal expression of LFA-1 could promote the occurrence and development of esophageal squamous cell carcinoma by regulating the expression of ICAM-3.