Abstract
Ascites-derived ovarian cancer stem cell (OCSC) populations may originate from the fallopian tube epithelium (FTE) or ovarian surface epithelium (OSE). Additionally, EpCAM/CD45 dual-positive OCSCs (DpOCSCs) may also result from the other origin. The distinctions between these two OCSC populations are not thoroughly understood. This study examines the transcriptome analysis of ascites-derived DpOCSC populations compared to ascites-derived OCSC populations with FTE/OSE origins. We observed that upregulated genes in DpOCSCs are primarily associated with inflammatory pathways, such as NFκB, TNF, Toll-like receptor, and IL-17 signaling pathways. Moreover, 14 out of 28 identified DpOCSCs-related hub genes were TCGA-validated at mRNA levels, among which SYK, CD74, and LCP1 were also validated at protein levels using the UALCAN dataset. SYK, in particular, stood out, displaying a noteworthy association with decreased progression-free survival. Notably, we found a significant positive correlation between DpOCSCs-related hub genes and immune checkpoint proteins, as well as with infiltrating immune-suppressive cells. Further examination of their relations with clinico-pathological features revealed that seven out of fourteen TCGA-validated hub genes were significantly linked to lymphatic and venous invasion, which were transcriptionally regulated by Wnt/β-catenin signaling pathway. Furthermore, SYK was significantly related to new neoplasm events type and primary therapy outcomes success. In conclusion, our findings suggest that hub genes associated with DpOCSC populations in ascites could be potential therapeutic targets due to their involvement in tumor progression and invasiveness.