Profiling of Breast Cancer Stem Cell Types/States Shows the Role of CD44hi/CD24lo-ALDH1hi as an Independent Prognostic Factor After Neoadjuvant Chemotherapy.
PMID 40943144 | PMCID PMC12428598 | DOI 10.3390/ijms26178219 · International journal of molecular sciences · 2025
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 (CD44hi/CD24lo, 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 CD44hi/CD24lo phenotype correlated with markers of EMT and PD-L1 expression, unlike ALDH1hi. Both Ep-CAMhi and CD24hi 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 CD44hi/CD24lo, Ep-CAMhi, and ALDH1hi phenotypes correlated with shorter overall survival (OS), CD24hi correlated with reduced disease-free survival (DFS). Interestingly, among all tested CSC markers, the CD44hi/CD24lo-ALDH1hi 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 CD44hi/CD24lo-ALDH1hi 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.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | CD24 | “In this study, six CSC markers (CD44hi/CD24lo, CD24, Ep-CAM, ALDH1, CD10, and BMI1) were assessed in a surgical cohort of 73 breast cancer patients.” | 0.98 | hgnc_dict_v1 |
| gene | BMI1 | “In this study, six CSC markers (CD44hi/CD24lo, CD24, Ep-CAM, ALDH1, CD10, and BMI1) were assessed in a surgical cohort of 73 breast cancer patients.” | 0.98 | hgnc_dict_v1 |
| gene | FOXP3 | “Both Ep-CAMhi and CD24hi 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).” | 0.98 | hgnc_dict_v1 |
| phenotype | breast cancer | “Profiling of Breast Cancer Stem Cell Types/States Shows the Role of CD44hi/CD24lo-ALDH1hi as an Independent Prognostic Factor After Neoadjuvant Chemotherapy.” | 0.98 | phenotype_alias_lexicon_v2 |
| population | Population | “In this study, six CSC markers (CD44hi/CD24lo, CD24, Ep-CAM, ALDH1, CD10, and BMI1) were assessed in a surgical cohort of 73 breast cancer patients.” | 0.80 | saudi_context_rules_v1 |