Table 1.
Marker | Function | Origin of Studied Cells | Reference | Association to Clinicopathological Features | Cell/Tissue Origin | Reference |
---|---|---|---|---|---|---|
CD44+ | Increased tumorigenicity, sphere-formation, cells self-renewal | Primary EOC tumors, cell cultures | [49,50,51,52] | Number of CD44+ cells higher in early stage EOC and correlated with shorter PFS Expression correlated with high-grade, advanced (III/IV FIGO) EOC in younger (<60) patients Higher number of CD44+ cells correlated with chemoresistance and shorter DFI CD44+ correlated with Ki67 index, p53 positivity and tumor grade in HGSOC, mucinous and endometroid EOC |
EOC-isolated cells Recurrent EOC (88% HGSOC) Primary and recurrent EOC (78% HGSOC) EOC (HGSOC 62%) and BOT |
[105,139,140,141] |
CD44 v6+ | Increased tumorigenicity, recapitulation of tumors | Xenotransplantation model | [57] | Distant metastases more frequent and metastasis free survival shorter in CD44v6+—high group of patients Increased number of CD44v6+ cells in primary tumors correlated with shorter OS |
EOC FIGO I–III tumors EOC FIGO III–IV tumors (71% HGSOC) |
[56,57] |
CD44+/MyD88+ | Increased tumorigenicity, sphere-formation, resistance to apoptosis, chemoresistance | Cell lines, ascites | [142] | Expression of MyD88 protein was an unfavorable prognostic factor for EOC patients | Benign ovarian tumors, BOT and EOC (54% HGSOC) | [97] |
CD44+/CD117+ | Increased tumorigenicity, sphere-formation, recapitulation of tumors, chemoresistance | EOC tumors, xenograft models | [49] | CD44+CD117+ cell lines were less prone to paclitaxel-induced apoptosis | EOC cell lines | [142] |
CD44+/CD24- | Increased tumorigenicity, sphere-formation | Cell lines | [143] | >25% CD44+/CD24- cells in ascites correlated with higher risk of recurrence and shorter PFS | Ascites-isolated cells from advanced EOC | [104] |
CD44+/CD24+/ EpCAM+ | Increased tumorigenicity, chemoresistance | Cell lines, EOC-isolated cell lines, ascites | [100,110] | Ovarian cancer stem cells expressing EpCAM+ are less prone to chemotherapy and are a source of recurrent tumor after the treatment | EOC I-IV FIGO stage (45% HGSOC, 14% clear cell, 17% endometroid, 12% mucinous) | [100] |
CD44+/CD166+ | Increased tumorigenicity, sphere-formation | Cell lines | [108] | Population of platinum-resistant cells is enriched in CD44+/CD166+ population | EOC-isolated and standard cell lines | [144] |
CD44+ALDH1+ | Increased tumorigenicity, chemoresistance | Cell lines | [145] | >50% ALDH1+ cells correlated with shorter OS | Advanced EOC (73% HGSOC) | [145] |
CD44+/CD133+/ALDH1A1+ | Chemoresistance | Cell lines, EOC-isolated cell lines | [116] | Expression of markers increased in recurrent compared to primary tumors | Advanced primary and recurrent EOC | [116] |
CD133+ | Increased tumorigenicity, enhanced vasculogenesis | Cell lines, EOC tumors, xenograft models, ascites | [72,78,81,146] | Expression of CD133+ correlated with presence of HGSOC, higher FIGO stage, ascites, chemoresistance, shorter PFS and OS No correlation with prognosis Expression of CD133+ correlated with shorter PFS and OS Expression of CD133+ correlated with shorter OS and platinum chemo-resistance |
EOC (67% HGSOC) EOC FIGO III–IV (72% HGSOC) Advanced metastatic HGSOC Advanced primary HGSOC |
[73,147,148,149] |
CD133+/ALDH1A+ | Increased tumorigenicity, cells self-renewal, chemoresistance | EOC tumors, cell lines, xenograft models | [80,81] | Expression of CD133+ correlated with III/IV FIGO stage, expression of CD133+/ALDH1A+ correlated with shorter PFS and OS | HGSOC | [150] |
CD117+ | Increased tumorigenicity, sphere-formation, recapitulation of tumors, chemoresistance | EOC-isolated cell lines, xenograft model, ascites | [62,63,64,151,152] | Expression of CD117+ correlated with shorter PFS 40% of HGSOC were CD117+ and expression correlated with chemoresistance |
Advanced metastatic HGSOC HGSOC |
[63,148] |
CD24+ | Increased tumorigenicity, stimulation of EMT | Cell lines | [92] | Expression of CD24+ correlated with FIG stage and the presence of peritoneal and lymph node metastases | 27% HGSOC 12% mucinous 18% clear-cell 18% endometaroid 23% others |
[92] |
BOT—borderline ovarian tumor; DFI—disease-free interval; EMT—epithelial-mesenchymal transition; EOC—epithelial ovarian cancer; FIGO—International Federation of Obstetrics and Gynecology; HGSOC—high-grade serous ovarian cancer; OS—overall survival; PFS—progression-free survival.