Table 1.
Cancer stem cell markers for prognosis of esophageal cancer.
Markers | Cancer Type EAC/ESCC | Results | Marker for Diagnosis or Prognosis | Reference |
---|---|---|---|---|
Single marker | ||||
CD44 | EAC ESCC |
Cell surface protein: contributes to tumor invasion and regulates EMT | High CD44 expression correlates to positive lymph node ratio and lymph vascular invasion | [29,30,31] |
ABCG2 | ESCC | ATP-binding cassette transporter (membrane transporter) is associated with the drug resistance and metastasis | The presence of ABCG2-positive cells was associated with poor survival independent of primary tumor size and positive lymph node metastasis | [33,46,47] |
ALDH1 | EAC ESCC |
Intracellular enzyme oxidizing aldehydes: ALDH1+ cancer cells possess highly invasive and metastatic capabilities with EMT phenotype and are associated with therapy resistances | Positive ALDH1 staining was relevant to higher clinical stage and shorter survival time | [43,44,45] |
CD133 | ESCC | Cell surface protein: promotes tumor initiation and self-renewal capacity as well as chemoresistance. | The presence of CD133+ cancer cells was associated with tumor cell differentiation | [32,33,34] |
CD271 | ESCC | Cell surface protein: CD271+ cancer cells possess higher self-renewal activity and are associated with therapy-resistance and lymphnode metastasis | Ep-CAM+ CD271(p75NTR)+ tumor cells in peripheral blood correlate with clinically diagnosed metastasis and venous invasion | [35,36,37] |
LgR5 | EAC | Cell surface protein: promotes proliferation, migration and invasion ability | High LgR5 was associated with worse survival | [38,39,40] |
CD90 | ESCC | Cell surface protein: CD90+ cells possess higher self-renewal activity and metastatic potential, and are more resistant to chemotherapy | Higher CD90 expression exhibit more local invasion and distant metastasis, indicating a poor prognosis | [41,42] |
ITGA7 | ESCC | Cell surface receptor: ITGA7 contributes to tumor innitiation and drug resistance, it promotes metastasis via inducing EMT together with an anti-apoptosis function. | More ITGA7+ cells in ESCC tissues predict a worse prognosis | [49] |
ICAM1 | ESCC | Intercellular adhesion molecule1: promotes cancer cell migration, invasion, EMT, sphere formation, tumorigenesis and drug resistance | [48] | |
SOX2 | ESCC | Transcription factor: promotes cancer cells migration and invasion as well as chemoresistance to cisplatin | Controversial results exist regarding the prognostic value of SOX2 because of opposite conclusion among studies | [53,54,55,56,57] |
NANOG | ESCC | Transcriptional regulator: regulates cancer cells proliferation and drug resistance | [58,59,60] | |
BMI-1 | ESCC | Transcriptional regulator: regulates radiosensitivity of tumor cells and inbitits cell growth and invasion | Overexpression of BMI-1 is associated with progression and invasion of EC | [61,62,63,64] |
OCT-4 | ESCC | Transcriptional regulator: promotes cell cycle progression and accelerates proliferation and invasion of esophageal cancer cells | Overexpression of OCT-4 is significantly associated with higher histological grade and poorer survival | [54,62,65,66] |
Ep-CAM | ESCC | Transmembrane glycoprotein: Ep-CAM contributes to cell proliferation and tumorigenesis | Expression level of Ep-CAM inversely correlates with degree of differentiation | [67,68,69] |
Gli-1 | EAC ESCC |
Transcription factor: promotes cell proliferation and is associated with chemoradiation resistance | Gli-1 is positively associated with distant metastasis, indicates poor outcome | [70,71,72] |
SALL4 | ESCC | Transcription factor: promotes cell proliferation, migration and invasion as well as chemoresistance to cisplatin, contributes to tumorigenesis in vivo | Overexpression of SALL4 was found in a majority of ESCC tissues and correlates with poor survival | [55,73] |
Podoplanin (PDPN) | ESCC | Transmembrane protein: accelerates the proliferation and regulates tumor EMT | PDPN expression at the edge of cancer cell nest associates with tumor invasion and poor prognosis | [74,75,76,77] |
Combined markers | ||||
CD44+/CD24− | EAC and ESCC | CD44+/CD24− EC cells exert a higher proliferation rate and mediate therapy resistance | [50] | |
CD44+/CD133+ | ESCC | Strong expression of CD44 and CD133 indicates a poor prognosis regardless of chemotherapy in ESCC | [51] | |
CD133+/CXCR4+ | ESCC | CD133+CXCR4+cells regulate tumor invasion and show high proliferative capacity | Concomitant CD133-CXCR4 expression heralds impaired disease-free survival and overall survival | [52] |