The Detection And Clinical Significance Of Circulating Tumor Stem Cells

Background: Breast cancer,one of the highest morbidity in women malignant tumors,is seriously threatening women's health.Tumor metastasis is the most common reason of death in cancer patients,clinically.It has been demonstrated that circulating tumor cells(CTCs)have a high correlation with tumor recurrence and metastasis,and cancer stem cells(CSCs)also play important roles in it.Currently,CTCs have been recognized to be an independent prognostic factor in breast cancer,and Epithelial mesenchymal transition(EMT)is an important way for CTCs' formation and developing to a metastatic tumor.Moreover,CSCs,for their unique characteristics such as self-renewal,pluripotent and drug resistence,have been proved to be one of the reasons to the recurrence and metastasis of some cancers.There are many ways to search CSCs,among which CD133 may be a reliable marker of breast cancer stem cells.Methods: 60 newly diagnosed breast cancer patients used CanPatrolTM system for CTCs detection.2 times of CTCs detection were respectively conducted before and after chemotherapy for identifying the subpopulations and measuring the CD133 expression of CTCs.Heterogeneity of CTCs was analyzing by Kruskal Wallis H test.Kaplan–Meier analyses and the log-rank test were used for survival analyses.P<0.05 were considered statistically significant.All statistical tests were two-sided.Results: At the baseline,CTCs were detected in 54 patients(90.0% in all60 patients),the median of CTCs was 7.5(16.8),among which the median of epithelial CTCs,the biophenotypic epithelial/mesenchymal CTCs and the mesenchymal CTCs were respectively 1.0(1.8),5.0(11.8)and 1.0(4.0).Under the analysis of CTCs heterogeneity,the proportion of CD133 positive CTCs was significantly large in biophenotypic epithelial/mesenchymal CTCs(54.8%),compared with epithelial CTCs(43.8%)and mesenchymal CTCs(47.1%)(P=0.048).The difference of CTCs subpopulations based on breast cancer subtypes was not significantly(P=0.087).Compared with other subtypes,the CD133 expression levels of CTCs in Luminal A patients were significantly the lowest(P=0.002)and that in Luminal B patients were the highest.For the CTCs results at baseline,neither the amount of CTCs nor proportion of CD133 positive CTCs in mesenchymal CTCs was associated with RFS.34 patients took a second CTCs detection after chemotherapy,we found that the patients whose proportion of CD133 positive CTCs in mesenchymal CTCs was high(?50%),were more probably to recurrence in short period(Log-rank test,P=0.021),especially in the patients who were not detected CD133 positive mesenchymal CTCs at baseline(Log-rank test,P=0.017).Conclusion:1 There is heterogeneity of CTCs in different breast cancer subtypes,and the CD133 expression levels of CTCs in Luminal B patients are the highest.2 The CD133 expression levels significantly differ among different CTCs subpopulations,and the proportion of CD133 positive CTCs is the largest in biophenotypic epithelial/mesenchymal CTCs.3 Breast cancer patients detected with high proportion of CD133 positive CTCs in mesenchymal CTCs after chemotherapy,are more probably to recurrence in short period.