| Research background:In recent years,breast cancer has developed into the first female tumor,accounting for 24.2%of the female tumor incidence.The incidence of breast cancer in China is on the rise,which poses a great threat to women's health.Breast cancer prevention and treatment needs to increase the proportion of early diagnosis so as to improve the overall prognosis.Circulating tumor cells(CTCs)are tumor cells that are shed from the primary tumor focus or metastatic focus and enter the circulatory system for various reasons.CTCs>1 in early breast cancer and CTCs>5 in advanced breast cancer suggest a poor prognosis(AJCC8th level ? evidence).CTCs can undergo epithelial-mesenchymal transformation(EMT)to obtain more mesenchymal properties.Interstitial CTCs represent a worse tumor prognosis.Metalloproteinase 9(MMP9)is a gelatinase that can degrade extracellular matrix,promote angiogenesis,promote tumor invasion and metastasis,assist CTCs to invade into the blood,and induce EMT.So,does high MMP9 expression directly lead to increased CTCs production and promote EMT of CTCs?Does the expression of MMP9 in CTCs show the same trend as that in pathological tissues,or is it different due to tumor heterogeneity?Objective:In this study,CTCs subtype and MMP9 expression were detected to explore the correlation between CTCs heterogeneity and MMP9 expression and clinical characteristics of breast cancer:To explore the correlation between the total number of CTCs and its subtypes and clinicopathology.To investigate the correlation between MMP9 expression and clinicopathology.To investigate the relationship between CTCs population and the expression of MMP9 in each CTCs subtype,and whether MMP9 affects the number of CTCs and their EMT.Methods:1.Venous blood was collected early in the morning before operation in 111 patients diagnosed with breast cancer who had not undergone surgery and other treatments.CTCs were detected by canmclultm and different subtypes were labeled by RNA probes.Patients were grouped according to clinical data,and independent sample t test or non-parametric test were performed using SPSS20.0 to compare the total number of CTCs and the distribution of CTCs among different groups..2.A total of 116 patients diagnosed with breast cancer who had pathological film were included.The pathological film was taken and the MMP9 immunohistochemical examination was performed.According to the MMP9 positive and weak groups of patients,SPSS20.0 was used to perform independent sample t test,one-way anova,and non-parametric test to compare the differences between clinical indicators of patients.3.76 patients diagnosed with breast cancer without surgery were included.Venous blood was collected early in the morning before surgery to detect CTCs,and the expression of MMP9 on CTC was detected at the same time.Postoperative pathology was performed to detect MMP9.Independent sample t test or non-parametric test were performed using SPSS20.0 to compare the expression of MMP9 between CTC groups according to the grouping.Results:CTCs formation was positively correlated with clinical stage,tumor diameter,lymph node metastasis and Ki-67(P<0.05).The number of mixed CTCs was positively correlated with clinical stage,tumor diameter and Ki-67(P<0.05).The number of interstitial CTCs increased with lymph node metastasis(P<0.05).There was no significant difference in the total number of CTCs and each subtype between the molecular typing groups(P>0.05).High MMP9 expression was positively correlated with increased lymph node metastasis(P<0.05).Low MMP9 expression was associated with increased tumor diameter(P<0.05).With the increase of MMP9 expression,the her-2 positive proportion first increased and then decreased(P<0.05).The positive rate of MMP9 expression in mixed CTCs was higher,and the proportion of MMP9 medium to high expression in mixed CTCs was higher than the other two types(P<0.05).High expression of MMP9 in tumor tissue can promote the formation of CTCs and EMT(P<0.05).High expression of MMP9 in tumor tissues resulted in an increase in the number of CTCs expressing MMP9(P<0.05).Conclusion:1.CTCs experienced EMT and had a high proportion.Later clinical stage,larger tumor diameter,more lymph node metastasis,and increased Ki-67 expression can lead to increased CTCs.Late clinical stage,large tumor diameter and increased Ki-67 expression could lead to the increase of mixed CTCs.The number of interstitial CTCs increased with lymph node metastasis.There was no significant difference in the total number of CTCs and the distribution of each subtype among the molecular typing groups.2.MMP9 expression was positively correlated with lymph node metastasis.MMP9 expression was negatively correlated with tumor diameter.The positive rate of HER-2 was not related to the high expression of MMP9.3.The positive rate of MMP9 expression in mixed CTCs was higher,and the proportion of MMP9 medium to high expression in mixed CTCs was higher than the other two types.High expression of MMP9 in tumor tissue can promote the formation of CTCs and EMT.High expression of MMP9 in tumor tissues resulted in an increase in the number of CTCs expressing MMP9. |
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