Identification of hub genes and key signaling pathways of ascites-derived ovarian cancer stem cells from different origins and associated with clinicopathological features

Ovarian cancer stem cells (OCSCs) are responsible for many epithelial ovarian cancer-related-clinical features, including tumor initiation and progression, metastasis, and recurrence. Ascites-derived OCSC populations could be originated from the fusion of cancerous cells with immune cells or the fallopian tube fimbriae. However, the differently expressed genes between OCSC populations from different origins are not well understood. Here we sought to identify the common hub genes and key signaling pathways related to ascites-derived OCSCs from different origins. At first, comprehensive transcriptomic analysis from two datasets GSE۹۰۱۲۵ (ascites-derived OCSC populations of fimbriae origin) and GSE۷۵۰۳۶ (ascites-derived OCSC population of fusion origin) was performed to find hub genes separately and in the next step, the common hub genes and signaling pathways were determined. The up-regulated genes from GSE۹۰۱۲۵ were mainly related to the migration and epithelial to mesenchymal transition and TGFβ , PI۳K-AKT, and Wnt signaling pathways. Whereas up-regulated genes from GSE۷۵۰۳۶ were mostly involved in cytokine production and inflammatory response and to NF k B and MAPK signaling pathways. We found ten common hub genes with amplification mutations associated with ascites-derived OCSC populations from different origins. Among the signaling pathways, the Wnt and TGFβ pathways are the most important pathways associated with these common hub genes. Clinicopathological evaluation of common hub genes showed that CD۴۴, CD۶۸, TGFBI, and ZEB۲ were significantly related to the lymphatic and venous invasion. While HIF۱A and VCAN were significantly related to the venous invasion. It is interesting to note that PPARG and VCAN were significantly related to new neoplasm event type and primary outcome success, respectively. In conclusion, we suggest that deciphering and targeting common hub genes between OCSCs from different origins could have an impact on epithelial ovarian cancer–related clinical features.

کلیدواژه ها:

Ovarian cancer stem cells ، ascites ، fimbriae ، immune cells ، Wnt signaling ، TGF signaling