乳腺癌干细胞类型/状态谱型分析揭示 CD44(hi)/CD24(lo)-ALDH1(hi) 作为新辅助化疗后独立预后因素的作用

Multiple markers exist for breast cancer stem cells (CSCs), which are believed to represent the phenotypes of various CSC types and/or states. The relationship between each CSC subpopulation/state and the primary hallmarks of cancer has not been sufficiently clarified. In this study, six CSC markers (CD44 hi /CD24 lo , CD24, Ep-CAM, ALDH1, CD10, and BMI1) were assessed in a surgical cohort of 73 breast cancer patients. The expression of a single or multiple CSC markers was correlated with clinicopathological parameters, including markers of immune evasion, proliferation, epithelial-mesenchymal transition (EMT), and survival. All CSC phenotypes, except for CD10, correlated with markers indicative of higher proliferation. The CD44 hi /CD24 lo phenotype correlated with markers of EMT and PD-L1 expression, unlike ALDH1 hi . Both Ep-CAM hi and CD24 hi breast cancer were associated with indicators of immune evasion, including PD-L1 expression, and the infiltration of FOXP3+ and PD-1+ tumor-infiltrating lymphocytes (TIL).

While the CD44 hi /CD24 lo , Ep-CAM hi , and ALDH1 hi phenotypes correlated with shorter overall survival (OS), CD24 hi correlated with reduced disease-free survival (DFS). Interestingly, among all tested CSC markers, the CD44 hi /CD24 lo -ALDH1 hi combination phenotype correlated with the worst DFS (HR 2. 8, p = 0. 014 in univariate/multivariate analysis) and OS ( p < 0. 001, HR 6. 4 in univariate and 5. 4 in multivariate analysis).

A side-by-side comparison of multiple CSC markers demonstrated the differential linkage of CSC phenotype/state with distinct features of breast cancer. This comparison demonstrates the advantage of the CD44 hi /CD24 lo -ALDH1 hi combination marker for prognostication, especially after neoadjuvant chemotherapy. In the future, distinct markers of CSCs can hopefully be leveraged to trace/monitor different disease characteristics or treatment outcomes.