Transcriptional profiles of different states of cancer stem cells in triple-negative breast cancer

Breast cancer stem cells (BCSCs) are thought to be responsible for tumor initiation, metastasis and relapse. Our group and others have described markers useful in isolating BCSCs just as aldehyde dehydrogenase positive (ALDH +) or CD24(-)CD44(+). In fact, cells which simultaneously express both sets of markers have the highest tumor initiating capacity. Although the transcriptomic profile of cells expressing each BCSC marker alone has been reported, the profile of the most tumorigenic population expressing both sets of markers has not. Here we used the biomarker combination of ALDH and CD24/CD44 to sort four populations isolated from triple-negative breast cancer (TNBC) patient-derived xenografts, and performed whole-transcriptome sequencing on each population. We systematically compared the profiles of the three states of BCSCs (ALDH(+)CD24(-)CD44(+), ALDH(+)non(-)CD24(-)CD44(+) and ALDH(-)CD24(-)CD44(+)) to that of the differentiated tumor cells (ALDH(-)non(-)CD24(-)CD44(+)). For the first time, we compared the ALDH(+)CD24(-)CD44(+) BCSCs with the other two BCSC populations. In ALDH(+)CD24(-)CD44(+) BCSCs, we identified P4HA2, PTGR1 and RAB40B as potential prognostic markers, which were virtually related to the status of BCSCs and tumor growth in TNBC cells.