Impact of homeobox genes in gastrointestinal cancer

Table 2 Aberrant expression of HOX and non-HOX genes in gastric cancer

Homeobox gene	Change	Underlying mechanism	Ref.
CDX2	↑ in complete IM > incomplete IM > dysplasia > GC	Promoter hypermethylation in GC	[27-29]
	Associated with differentiated type GC	Decreased intake of green tea or cruciferous vegetables
ISX	↑ in IM and GC	Increase of cyclin D1 and CD44	[31]
	Upregulated in undifferentiated type GC
PROX1	↑ in GC	Inhibition of apoptosis, promoting lymphangiogenesis and angiogenesis	[32]
	Associated with undifferentiated type, advanced stage and poor OS
PRRX1	↑ in GC	Induction of Wnt/β-catenin	[33]
	Associated with advanced stage and distant metastasis
IRX1	↓ in GC	Promoter hypermethylation	[35]
PDX1	↓ in GC	Promoter hypermethylation, histone hypoacetylation	[34,36,37]
	↑ in pseudopyloric gland IM
	Inversely related with advanced T/ N stage and undifferentiated type GC
HOXA13	↑ in GC	Not presented	[38]
	Associated with advanced TNM stage, undifferentiated type and poor response to chemotherapy
HOXB5	↑ in GC	Upregulation of β-catenin	[39]
HOXB7	↑ in primary or metastatic cancer than chronic gastritis or IM	Modulation of PI3K/Akt/PTEN axis	[41,42]
	Associated with advanced TNM stage and undifferentiated type GC
HOXD10	↓ in GC	Promoter hypermethylation	[40]
		Induction of IGFBP3

Note: PROX1, PRRX1, HOXA13 and HOXB7 are associated with advanced TNM stage, while PDX1 is inversely associated; ISX, PROX1, HOXA13 and HOXB7 are associated with undifferentiated type GC. IM: Intestinal metaplasia; GC: Gastric cancer; OS: Overall survival; PI3K: Phosphatidylinositol-3 kinase; IGFBP3: Insulin like growth factor binding protein 3.