CXC family of chemokines as prognostic or predictive biomarkers and possible drug targets in colorectal cancer

Table 1 CXC chemokines as biomarkers

Biomarker	Cancer type	Expression	Where is it measured?	Treatment	Predictive value	Ref.
CXCL1/2	Breast cancer	High	Paraffin embedded tissue	Chemoresistance 5FU	Poor	[17]
CXCL1	CRC	High	Tumor and cell lines	OXA + CURCUMIN	Poor	[18]
CXCL1/8 CXCR2	CRC, Prostate cancer	High	Cell lines and in vivo	OXA + SCH-527123	Poor	[22,24]
CXCL8	CRC	Low	Serum	Chemotherapy + Bevacizumab	Good	[25,26]
CXCL8	Breast cancer	Polymorphism, TT genotype	Peripheral blood (DNA)	FOLFOX+ Bevacizumab vs FOLFOX alone	Good	[26]
CXCR1	CRC	Polymorphism	Whole blood (DNA)	OXA based + Bevacizumab	Good	[27]
CXCL7/8 CXCR2	CRC	High	mRNA levels tumors	Surgery + ady vs Ady alone	Poor	[28]
CXCR4	CRC	Colocalization-Lgr5	CRC cell lines and tumors		Poor	[35]
CXCR4	CRC	Colocalization-CD133	CRC cell lines and in vivo	5FU; 5FU and OXA	Poor	[36,38]
CXCR4-microbiota	CRC	High	in vivo and in vitro	Lipopolysaccharides	Poor	[39]
CXCL12-visfatin	CRC	Interaction	CRC cells		Poor	[40]
CXCR4	CRC	High	Paraffin embedded tissue	Patients that underwent hepatectomy	Poor	[41]
CXCR4	CRC	High	CRC cells	OXA or 5FU therapies including anti-VEGF	Poor	[46]
CXCL10-KRAS mut	CRC CMS2 and CMS3	Low	TCGA, tumors		Poor	[52]
CXCL10	CRC	High	CRC cells, tumors, in vivo		Good	[53]
CXCL10	CRC	Expression	Post-surgical localized CRC		Good	[53,56]
CXCR3	CRC	High	Protein levels in primary tumors		Poor	[57]
CXCL10/11	CRC	High	Serum		Poor	[58]
CXCL9/10	CRC	High	in vivo	Anthracyclines + STAT KO	Good	[60]
CXCL9/10/11	Rectal cancer	High	mRNA levels tumors	5FU + Radiotherapy	Good	[64,65]
CXCL4	CRC	High	in vivo	5FU	Poor	[66]
CXCL13 CXCR5	CRC	High	Plasma levels and paraffin embedded tissue		Poor	[69,70]
CXCL13-microbiota	CRC	High	Tumors		Good	[71]
CXCR5⁺ CD8⁺ T cell	CRC	Presence	Tumors		Good	[73]
CXCL13	CRC	Low	mRNA levels tumors		Good	[56,74]
CXCL16	CRC	High	Serum		Poor	[81]
CXCL17	CRC	High	mRNA levels cell lines and tumors		Poor	[87]

CRC: Colorectal cancer; OXA: Oxaliplatin; VEGF: Vascular endothelial growth factor; 5FU: 5 Fluorouracil; KO: Knock out.

Table 2 The CXC chemokines and their receptors

CXC ligand	Chemokine name	Receptor	ELR domain
CXCL1	Growth-regulated oncogene (Gro-α)	CXCR2	ELR+
CXCL2	Growth-regulated oncogene (Gro-β)	CXCR2	ELR+
CXCL3	Growth-regulated oncogene (Gro-γ)	CXCR2	ELR+
CXCL4	Platelet factor-4 (PF-4)	CXCR3	ELR⁻
CXCL5	Epithelial cell-derived neutrophil-activating peptide-78 (ENA-78)	CXCR2	ELR+
CXCL6	Granulocyte chemotactic protein-2 (GCP-2)	CXCR1/2	ELR+
CXCL7	Neutrophil-activating peptide-2 (NAP-2)	CXCR2	ELR+
CXCL8	Interleukin-8 (IL-8)	CXCR1/2	ELR+
CXCL9	Monokine induced by interferon-γ (Mig)	CXCR3	ELR⁻
CXCL10	Inducible protein-10 (IP-10)	CXCR3	ELR⁻
CXCL11	Interferon-inducible T cell alpha chemoattractant (I-TAC)	CXCR3/7	ELR⁻
CXCL12	Stromal cell-derived factor-1 (SDF-1)	CXCR4/7	ELR⁻
CXCL13	B cell-attracting chemokine-1 (BCA-1)	CXCR5	ELR⁻
CXCL16	Scavenger receptor that binds phosphatidylserine and oxidized lipoprotein (SR-PSOX)	CXCR6	ELR⁻
CXCL17	VEGF-correlated chemokine-1 (VCC-1)	CXCR8	ELR+

VEGF: Vascular endothelial growth factor.