Table 1. Putative biomarkers of liver CSCs.
| Biomarker | Location | Biological functions in liver CSCs | Characteristics of marker-positive CSCs (Sources) | Refs |
|---|---|---|---|---|
| ABCG2 | Cell surface | Determinant of the SP phenotype; extruding a variety of compounds such as anticancer agents | Chemoresistant (PLC5, HepG2, Huh-7, MHCC-97L, Hep3B; Human HCC tissue) | [32–34] |
| AFP | Cytoplasm; secreted | Serum transport protein; binding numerous molecules (fatty acids, estrogen, steroids); modulating immune function, metabolism | Poorly differentiated, anti-apoptosis, cell cycle progression, tumorigenic, invasive, metastatic (Huh-1, HepG2, Hep3B, SK-Hep-1; Human HCC tissue; female athymic nude mice) | [35–38] |
| ALDH1 | Cytoplasm | Catalyzing the oxidation of endogenous and exogenous aldehydes; functional marker of CSCs; cellular detoxification | Abnormal metabolism, chemoresistant, tumorigenic (H2P, H2M, Hep3B, QGY-7701, QGY-7703, BEL7402, HepG2, PLC8024, Huh-7; SCID mice) | [39, 40] |
| CD13 | Cell surface | Reducing ROS-induced DNA damage; protecting cells from apoptosis | Tumorigenic, chemoresistant (Huh-7, PLC/PRF/5; Human HCC tissue; NOD/SCID mice) | [41–43] |
| CD24 | Cell surface | Mediating Twist2/STAT3/Nanog self-renewal pathway | Tumorigenic, chemoresistant, metastatic (HLE, HepG2, MHCC-97L, MHCC-LM3, MHCC-97H, Huh-7, PLC/PRF/5, Hep3B, BEL7402; Human HCC tissue; NOD/SCID mice) | [44–46] |
| CD44 | Cell surface | Reducing ROS level via stabilizing xCT; regulating TGF-β-mediated mesenchymal phenotype; mediating c-Met-PI3K-AKT signaling cascade | Tumorigenic, invasive, circulating (PLC/PRF/5, Huh-7, HLE, Huh-1, Hep3B, HepG2, SK-Hep-1, MHCC97-H, HLF; Human HCC tissue; Transgenic mice, Nude mice) | [47–51] |
| CD90 | Cell surface | Involved in cell-cell, cell-matrix interactions | Tumorigenic, invasive, metastatic, circulating, chemoresistant, proliferation (Hep3B, MHCC-97L/H, Huh-7, SMMC7721, SK-Hep-1, PLC/PRF/5; NOD/SCID mice; Human HCC tissue) | [52–54] |
| CD133 | Cell surface | Supporting tumor growth and survival; mediating Akt/PKB pathway and Neurotensin/Interleukin-8/CXCL1 signaling | Tumorigenic, chemoresistant (Hep3B, Huh-7, PLC8024, HepG2, SK-Hep-1; Human HCC tissue; SCID mice) | [28, 55–58] |
| CK19 | Cytoplasm | Skeleton protein | Tumorigenic, invasive, metastatic, chemoresistant (Huh-7, PLC/PRF/5, Hep3B; Human HCC tissue; NOD/SCID mice) | [59–61] |
| DCLK1 | Whole cell | Catalyzing tubulin polymerization into microtubules; regulating HCV replication | Tumorigenic, invasive, metastatic (Huh-7; Athymic nude Balb/c mice; Human HCC tissue) | [62, 63] |
| DLK1 | Cell surface | Not reported | Tumorigenic, chemoresistant (PLC/PRF/5, QGY7701, SK-Hep-1, YY-8103, SMMC7721, HepG2, Hep3B, Huh-7, SNU398, WRL68, MHCC-97L, MHCC-LM3; NOD/SCID mice) | [64] |
| EpCAM | Cell surface | Cell-cell adhesion; maintenance of a pluripotent state; regulation of differentiation, migration and invasion | Tumorigenic, invasive, chemoresistant, circulating (Huh-7, Huh-1, Hep3B, PLC/PRF/5, SK-Hep-1, HLE, HLF; Human HCC tissue) | [37, 38, 52, 65–67] |
| KIAA1114 | Cell surface | Not reported | Tumorigenic, metastatic (Hep3B, SK-Hep-1, Huh-7, HepG2, SH-J1, SNU475; Beige/nude/XID mice; Human HCC tissue) | [68] |
| Lin28B | Nucleus (main) | Regulating the transition between pluripotency and committed cell lineages | Metastatic, poorly differentiated, circulating (PLC/PRF/5, Huh-7, HepG2; Human HCC tissue; Transgenic mice) | [69–71] |
| OV6 | Cell surface | Not reported | Tumorigenic, chemoresistant, invasive, metastatic (Huh-7, SMMC7721, HepG2, PLC/PRF/5, Hep3B; Human HCC tissue; NOD/SCID mice) | [72–74] |
| SALL4 | Intracellular | Regulating embryogenesis, organogenesis, pluripotency | Cell cycle progression, chemoresistant (Huh-7, PLC/PRF/5; NOD/SCID mice; Human HCC tissue) | [75, 76] |
| TLR4 | Cell surface | Receptor for LPS; facilitating invasion and migration | Invasive, metastatic (SMMC7721, Huh-7; Human HCC tissue; BALB/c-nu/nu mice) | [77, 78] |
Abbreviations: ABCG2, ATP-binding cassette G subfamily type 2 transporter; SP, side population; ALDH1, Aldehyde dehydrogenase 1; DCLK1, doublecortin-like kinase 1; SALL4, Sal-Like Protein.