Significance of breast cancer stem cell surface markers in predicting chemotherapy sensitivity and recurrence / 国际外科学杂志

ABSTRACT

Objective:To analyze how the surface marker of breast cancer stem cell related to chemotherapy resistance and postoperative recurrence.Methods:The GEO public database GSE25066 and GSE32603 were used to extract clinical data including pathological evaluation of neoadjuvant chemotherapy, postoperative follow-up recurrence and recurrence time, and the expression levels of the following 18 breast cancer stem cell marker genes were extracted CD44, CD24, EPCAM, CD49f, PROM1, CD61, ALDH1A1, CD10, ALDH1A3, ABCG2, RANK, CD47, CD166, SLUG, SOX2, SXO9, SOX10, MYC. A total of 488 patients with GSE25066 were divided into pathology compete response(pCR) group ( n=99) and residual disease (RD) group ( n=389) according to the pathological analysis. Another 418 patients with complete recurrence data was divided into recurrence group ( n=111) and non-recurrence group ( n=307), they were used for prognosis analysis. The effects of each tumor stem cell marker on chemotherapy sensitivity and tumor recurrence were analyzed by logistic, lasso and COX regression. The gene expression level of GSE32603 before and after neoadjuvant chemotherapy were used to analyze the changes after neoadjuvant chemotherapy in 166 patients, to determine the enrichment effect of chemotherapy on stem cells. Results:In chemotherapy response analysis, tumor stem cell markers CD44( OR=0.78, 95% CI 0.63-0.98) and SANI2 ( OR=0.80, 95% CI 0.68-0.93) were negatively correlated with neoadjuvant chemotherapy sensitivity, and CD24( OR=1.18, 95% CI 0.97-1.47) was positively correlated with chemosensitivity. In the recurrence correlation analysis, the patients with CD44 + ( OR=1.22, 95% CI 0.98-1.51), CD24 low( OR=0.94, 95% CI 0.79-1.11) and SANI2( OR=1.17, 95% CI 1.00-1.37) expression have a high recurrence rate. As chemotherapy progressed, the MME, CD49f, SOX10, MYC, and SOX9 ( P<0.05) showed an enrichment process. Conclusions:Breast cancer stem cell markers CD44 + CD24 - and SLUG can be used to predict the efficacy of neoadjuvant chemotherapy and recurrence after tumor treatment. They are relatively stable marker for studying breast cancer stem cells.