The Expression Of MMP-9 And VEGF In Colon Cancer And The Clinical Significance Of TANs Infiltration

Objective:To explore the relationship between matrix metalloproteinase-9(MMP-9),vascular endothelial growth factor(VEGF),tumor-associated neutrophils(TANs)and the clinicopathological characteristics of colon cancer.And the correlation between the positive rate of MMP-9,VEGF expression and TANs infiltration density in colon cancer tissues.Provide more theoretical basis for the related research on the occurrence,development,metastasis and prognosis of colon cancer.Methods:Collect 54 colon specimens from colon cancer patients who underwent surgery in the Department of Oncology,the First Affiliated Hospital of Kunming Medical University from July 2019 to June 2020.Each specimen contains colon cancer tissue and para-cancerous tissue.The diagnostic criteria for all patients are based on TNM staging(UICC/AJCC 8th edition TNM staging).Inclusion criteria:The patient was diagnosed as colon cancer by pathological results.None of the patients received radiotherapy,chemotherapy,or targeted therapy before surgery.The patient’s clinical data was complete;the patient volunteered to participate in this study.Exclusion criteria:patients with advanced colon cancer have symptoms such as acute intestinal obstruction or bleeding.Patients with advanced colon cancer have multiple organ dysfunctions such as liver and heart.Patients with allergies and skin prone to bleeding.Pregnant or breastfeeding women and female patients of childbearing age.Immunohistochemistry(S-P method)was used to detect the expression of MMP-9,VEGF,and CD66b in colon cancer tissues.The tumor-associated neutrophils were labeled with CD66b,and TANs were counted.Chi-square test and Fisher’s exact test were used.Single factor analysis was used to analyze the correlation of each index,and the Spearman method was used for correlation analysis.Results:1.The expression of MMP-9 in colon cancer tissues and adjacent tissues of colon cancer:The positive rate of MMP-9 expression in colon cancer:63.0%(34/54),and the positive rate of expression in adjacent tissues:11.1%(6/54),the difference between the two groups was statistically significant(χ2=31.129 P<0.05),indicating that the expression of MMP-9 in colon cancer tissue was significantly higher than that in adjacent tissues.2.The expression of VEGF in colon cancer tissues and adjacent colon cancer tissues:The positive rate of VEGF expression in colon cancer:(36/54)66.7%,and the positive rate of expression in adjacent tissues:13.0%(7/54),the difference between the two groups was statistically significant(χ2=32.497 P<0.05),indicating that the expression of VEGF in colon cancer tissue was significantly higher than that in adjacent tissues.3.Infiltration density of TANs in colon cancer tissues and adjacent colon cancer tissues:The high density rate of TANs in colon cancer:63.0%(34/54),and the high density rate in adjacent tissues:18.5%(10/54),The difference between the two groups was statistically significant(χ2=21.222 P<0.05),indicating that the density of CD66b+TANs in colon cancer tissues was significantly higher than that in adjacent tissues.4.The relationship between the positive rate of MMP-9 expression in colon cancer tissues and the clinicopathological characteristics of colon cancer:The relationship between the expression of MMP-9 in 54 cases of colon cancer tissue and the clinicopathological parameters was analyzed,and it was found that the positive rate of MMP-9 expression was in the infiltration depths of T1-T2 and T3-T4 were 0%(0/8)and 73.9%(34/46),and the difference was statistically significant(P=0.000).The positive rate of MMP-9 expression in tumors Diameter>4cm and-4cm are respectively:85.7%(24/28),38.5%(10/26),the difference is statistically significant(x2=12.908 P=0.000).Colon cancer with MMP-9 metastasis to lymph nodes The positive rate of expression in tissues was significantly higher than that of those without lymph node metastasis,and the difference was statistically significant(χ2=4.195 P=0.041).The positive rates of expression in TNM stages Ⅰ-Ⅱ and Ⅲ-Ⅳ of MMP-9 tumors were 53.8%(21/39),86.7%(13/15),the difference was statistically significant(χ2=5.004 P=0.025).It showed that the positive rate of MMP-9 expression was related to the depth of invasion,tumor diameter,lymph node metastasis,and TNM staging of colon cancer patients(P<0.05),and was not related to the age,gender,tumor location,degree of differentiation,and distant metastasis of colon cancer patients(P>0.05).5.The relationship between the positive rate of VEGF expression in colon cancer tissues and the clinicopathological characteristics of colon cancer:The relationship between the expression of VEGF in 54 cases of colon cancer tissues and the clinicopathological parameters was analyzed,and it was found that the positive rate of VEGF expression was at the depth of invasion T1-T2.T3-T4 were:0%(0/8),78.2%(36/46),the difference was statistically significant(P=0.000).The positive rate of VEGF expression in tumor diameter>4cm,≤4cm were 85.7%(24/28)and 46.2%(12/26),the difference was statistically significant(χ2=9,495 P=0,002).The positive rate of VEGF expression in colon cancer tissues with lymph node metastasis was significantly higher than that in those without lymph node metastasis.The difference was statistically significant(P=0.021).The positive rates of TNM stages Ⅰ-Ⅱ andⅢ-Ⅳ of VEGF tumors were 56.4%(22/39)and 93.3%(14/15),respectively,the difference was statistically significant(χ2=6.645 P=0.010).It shows that the positive rate of VEGF expression is related to the depth of invasion,tumor diameter,lymph node metastasis,and TNM staging of colon cancer patients(P<0.05),but has nothing to do with the age,gender,tumor location,degree of differentiation,and distant metastasis of colon cancer patients(P>0.05).6.The relationship between the infiltration density of TANs in colon cancer tissues and the clinicopathological characteristics of colon cancer:The relationship between CD66b+ TANs and clinicopathological characteristics in 54 cases of colon cancer tissues was analyzed,and it was found that the high density of CD66b+TANs was at the depth of invasion T1-T2,T3-T4 are respectively:0%(0/8),72%(33/46),the difference is statistically significant(P=0.000).The high density rate of CD66b+TANs in the tumor diameter>4cm,≤4cm were 78.6%(22/28),42.3%(11/26),the difference was statistically significant(χ2=7.460 P=0.006).CD66b+TANs in the lymph node metastasis colon cancer tissue has a significant high density rate Higher than those without lymph node metastasis,the difference was statistically significant(χ2=8.015 P=0.005).The high density rates of CD66b+TANs in TNM stages Ⅰ-Ⅱ and Ⅲ-Ⅳ were 49%(19/39),93%(14/15),the difference was statistically significant(χ2=9.074 P=0.003).It showed that the infiltration density of CD66b+TANs was related to the depth of invasion,tumor diameter,the presence or absence of lymph node metastasis,and TNM staging(P<0.05).It was not related to the age,gender,tumor location,degree of differentiation,and distant metastasis of colon cancer patients(P>0.05).7.Correlation between TANs infiltration density and MMP-9 expression in colon cancer tissues:Among the 34 cases of high-density CD66b+TANs infiltrating colon cancer tissues,26 cases have high MMP-9 expression.Among the 20 cases of low-density CD66b+TANs infiltrating colon cancer tissues,12 cases have low MMP-9 expression.Spearman analysis showed that the infiltration density of CD66b+TANs was positively correlated with the expression of MMP-9(rs=0.411 P=0.002).8.Correlation between TANs infiltration density and VEGF expression in colon cancer tissues:Among the 34 cases of high-density CD66b+TANs infiltrating colon cancer tissues,30 cases of high-expressing VEGF.Among the 20 cases of low-density CD66b+TANs infiltrating colon cancer tissues,14 cases of low-expressing VEGF.Spearman analysis showed that the infiltration density of CD66b+TANs was positively correlated with the expression of VEGF(rs=0.483 P=0.000).9.Correlation between the expression of MMP-9 and VEGF in colon cancer tissues:Among the 34 cases of colon cancer with high expression of MMP-9 protein,34 cases of colon cancer with high expression of VEGF protein.Among the 20 cases of colon cancer with low expression of MMP-9 protein,18 cases of colon cancer with low expression of VEGF protein.Spearman analysis showed that the expression of MMP-9 and VEGF in colon cancer was positively correlated(rs=0.922 P=0.000).Conclusion:1.The expression of MMP-9 and VEGF in colon cancer tissue is significantly higher than that in adjacent tissues of colon cancer,and the infiltration density of TANs in colon cancer tissue is significantly higher than that in adjacent tissues of colon cancer,suggesting that MMP-9,VEGF and TANs may be involved in the occurrence of colon cancer,development process.2.In colon cancer tissue,MMP-9,VEGF,TANs are related to tumor invasion depth,tumor diameter,lymph node metastasis and TNM staging,suggesting that MMP-9,VEGF,TANs are related to the possible invasion and metastasis of colon cancer.3.The infiltration density of TANs in colon cancer is positively correlated with the positive expression rate of MMP-9 and VEGF,suggesting that TANs can promote tumor growth and metastasis by secreting MMP-9 and VEGF,4.The expression of MMP-9 and VEGF in colon cancer is positively correlated,indicating that MMP-9 and VEGF have a synergistic effect in the occurrence and development of colon cancer.5.The detection of TANs,MMP-9 and VEGF may be used to predict the development trend of colon cancer and the prognosis of colon cancer,assist in the selection of treatment options for colon cancer,but a larger sample of experimental studies is needed to prove it.