Expression profile of stem cell pathway genes in patients with advanced breast cancer after neoadjuvant therapy

Abstract

Presence of breast cancer stem cells (BCSCs) is one of reasons for therapy resistance and metastatic development. Currently, neoadjuvant therapy is widely applied for local advanced breast cancer prior to tumor resection. This study aimed to analyze existence of BCSCs after neoadjuvant therapy and determine their correlation with clinical characteristics and patient survival. Cancer tissues were collected from 46 patients with stage IIIb or IV breast cancer before and after chemotherapy or hormone neoadjuvant therapy. The expression profiles of stem cell pathway genes were then investigated using next generation sequencing (Miseq, Illumina) and TruSeq Targeted RNA Expression stem cell panel kit (Illumina) comprising 100 genes. Altered stem cell gene expression was analyzed using paired t-test and correlated with clinical characteristics. Twelve stem cell pathway genes were significantly altered after neoadjuvant therapy, comprising six upregulated genes (ALDH1A1, ALDH2, CCND2, CXCL12, FZD7, and IGF1) and six downregulated genes (CCNE1, CDC42, CTNNB1, HDAC2, PSEN1, and PSENEN). We observed a significant increase in ALDH1A1 in the 3-year non-survival group and a poor survival rate of patients in high CDC42 and HDAC2 expression group. It can be concluded that overexpression of ALDH1A1, CDC42, and HDAC2 after neoadjuvant chemotherapy is correlated with poor prognosis in advanced breast cancer.