Is there a genetic signature for liver metastasis in colorectal cancer?

Table 1 Summary of gene expression profile studies related to CRC liver metastasis

Source for transcription profile comparisons	Authors	Signature	Prediction
Primary tumors (Stage II and III)	Bertucci et al[11]	46 gene set	Lymph Node (+)
Primary tumors (Dukes C)	Arango et al[12]	Two different gene sets	Survival
Primary tumors (Stage II and III)	Barrier et al[13]	30 gene set	Lymph Node (+)
Primary tumors (Stage II and III)	Komuro et al[14]	Gene set	Stage Classification
Primary tumors (Stage II and III)	Kwon et al[15]	60 gene set	Lymph Node (+)
Primary tumors (Dukes B)	Wang et al[16]	23 gene set	Recurrence
Primary tumors (Stage II to IV)	D´Arrico et al[17]	37 gene set	Distant Recurrence
Primary tumors and matched metastases	D´Arrico et al[17]	GnT-IV gene1	Liver Metastasis
Primary tumors and matched metastases	Koehler et al[18]	Not found	Liver Metastasis
Primary tumors and matched metastases	Agrawal et al[20]	11 gene set	Metastasis (including liver)
CRC cell lines2	Hegde et al[21]	11 gene set	Metastatic potential
CRC cell lines2	[11-14,16,17,22]	Individual genes3	Metastatic potential

¹Mannosyl (alpha-1, 3-)-glycoprotein beta-1, 4-N-acetyl-glucosaminyl-transferase, which was found up-regulated in CRC liver metastases compared to primary CRC tumors;

²Comparing SW480 to SW620;

³Down-regulation of Cadherin 17 (CDH17)[11,22], Insulin-like growth factor 2 (IGF2)[14,17], Tyrosine 3-monooxygenase/tryptophan-5-monooxygenase activation protein (YWHAH)[12,16], DEK oncogene (DEK)[11,12] and GATA binding protein (GATA6)[11,14], up-regulation of Linker for activation of T cells (LAT)[14,16] and Protein Kinase, cAMP dependent, catalytic alpha (PRKACA)[12,14], and altered expression of IQ motif containing GTPase activating protein 1 (IQGAP1)[11,12], Tumor protein 53 (TP53)[11,12], Oligoadenylate synthetase 1 (OAS1)[11,12], Interferon regulatory factor (IRF2)[11,14], Retinoic acid receptor beta (RARB)[11,12] and Programmed cell death 10 (PDCD10)[12,13].

Table 2 Proteins related to liver metastasis formation and their function, and their differential expression when comparing primary tumors and liver metastasis by immunohistochemical technique

Proteins related to liver metastasis formation	Function	Liver expression compared to primary tumor (IHC)
E-Cadherin	Adhesion	Down-regulated[34]
Epithelial Cell Adhesion Molecule (EpCAM)	Adhesion	NA
P-Selectin and L-Selectin	Adhesion	NA
Carcinoembryonic Antigen (CEA)	Adhesion	NA
Integrin αvβ5	Adhesion, Survival	NA
sLex and sLea	Adhesion	Up-regulated[48,51]
Osteopontin (OPN)	Adhesion, Survival, Motility	Up-regulated[63]
Intracellular Adhesion Molecule (ICAM-1)	Adhesion	NA
Vascular Cell Adhesion Molecule (VCAM-1)	Adhesion	NA
CD44v6	Adhesion	NA
Cathepsine B	Invasion	NA
MMP-7	Invasion	Up-regulated[81]
MMP-2 and MMP-9	Invasion	Up-regulated[86]
Angiopoietin	Angiogenesis	Up-regulated[110]
Epidermal Growth Factor Receptor	Growth	Equal[125]
Urokinase Plasminogen Activator Receptor (uPAR)	Invasion, Motility, Dormancy	NA
Vascular endotelial Growth Factor (VEGF)	Angiogenesis	Equal[109]
Thrombospondin-1 (TSP-1)	Angiogenesis	NA
Angiostatin	Angiogenesis	NA
Endostatin	Angiogenesis	NA
Thimidine Phosphorylase (dThdPase or PDECGF)	Angiogenesis	NA
c-erb-2	Growth	NA
c-Src/β-Arrestin 1	Growth	NA
FAS Receptor (CD95)	Apoptosis	Down-regulated[134]
TRAIL Receptors (-R1, -R2, -R3 and -R4)	Apoptosis	NA
Nm23-H1 and Nm23-H2	Metastasis Suppresor Genes	NA
PRL-3	Motility, Extravasation	Up-regulated[157]

NA: Not available.