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. 2020 Jun 17;9(6):1481. doi: 10.3390/cells9061481

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]