Impact of homeobox genes in gastrointestinal cancer

Table 3 Aberrant expression of HOX and non-HOX genes in colorectal cancer

Homeobox gene	Change	Underlying mechanism	Ref.
CDX1	↑ in adenomatous polyp, ↓ in CRC	Regulation of cyclin D1 and β-catenin/TCF pathway	[55,56,58]
		Regulated by miR-215
CDX2	↓ in adenoma and CRC	Loss of Mucdhl	[50-55]
	Inversely associated with right side tumor, poorly differentiated type, advanced stage, poor prognosis, CIMP, MMR-deficient tumor	Induction of Wnt/β-catenin axis
ALX4	↓ in dysplasia and CRC	Promoter hypermethylation	[59]
PROX1	↑ in CRC	Induction of β-catenin/TCF axis	[60,61]
	Associated with advanced stage and lymph node metastasis	Inhibition of E-cadherin activity
HOXA4, D10	↑ in CRC	Stem cell overpopulation and crypt renewal	[63]
HOXA5, A9, A10, C6	Proximal colon tumor > distal colon tumor	Not presented	[64]
HOXB13	Distal colon tumor > proximal colon tumor	Not presented	[64]
HOXB7	↑ in CRC	Activation of PI3K/Akt and MAPK pathways	[67]
	Associated with advanced stage, T stage, distant metastasis and poor OS

CRC: Colorectal cancer; TCF: β-catenin/T-cell factor; CIMP: CpG island methylation phenotype; OS: Overall survival; PI3K: Phosphatidylinositol-3 kinase; MAPK: Mitogen-activated protein kinase.