Copyright ©The Author(s) 2016.
World J Gastroenterol. Oct 7, 2016; 22(37): 8247-8256
Published online Oct 7, 2016. doi: 10.3748/wjg.v22.i37.8247
Table 1 Aberrant expression of HOX and non-HOX genes in esophageal cancer
Homeobox geneChangeUnderlying mechanismRef.
CDX2↑ in BE/EACConcomitant decrease of PITX1[12,13]
No difference between BE and EACAssociation with β-catenin
HOXB5, B6, B7↑ in BE/dysplasia/EACInduction of intestinal markers such as KRT20, Muc2 and villin[15]
CDX2↓ in a ESCC cell line and tissuesPromoter hypermethylation[18]
MEIS↓ in ESCC, inversely related with nodal status and high tumor stageConcomitant increase of SOX2[24]
HOXA7, A9, C6↑ in ESCCNot presented[16]
HOXA5, A10, B13, C6, C10, C13, D3↑ in BE/EAC, highest in T2 stageNot presented[17]
HOXA13↑ in ESCC, associated with OS and DFSTargeting annexinA2, MnSOD, ERAB[19-21]
HOXB7↑ in ESCC, associated with T/N stage and DFSNot presented[23]
Table 2 Aberrant expression of HOX and non-HOX genes in gastric cancer
Homeobox geneChangeUnderlying mechanismRef.
CDX2↑ in complete IM > incomplete IM > dysplasia > GCPromoter hypermethylation in GC[27-29]
Associated with differentiated type GCDecreased intake of green tea or cruciferous vegetables
ISX↑ in IM and GCIncrease of cyclin D1 and CD44[31]
Upregulated in undifferentiated type GC
PROX1↑ in GCInhibition of apoptosis, promoting lymphangiogenesis and angiogenesis[32]
Associated with undifferentiated type, advanced stage and poor OS
PRRX1↑ in GCInduction of Wnt/β-catenin[33]
Associated with advanced stage and distant metastasis
IRX1↓ in GCPromoter hypermethylation[35]
PDX1↓ in GCPromoter hypermethylation, histone hypoacetylation[34,36,37]
↑ in pseudopyloric gland IM
Inversely related with advanced T/ N stage and undifferentiated type GC
HOXA13↑ in GCNot presented[38]
Associated with advanced TNM stage, undifferentiated type and poor response to chemotherapy
HOXB5↑ in GCUpregulation of β-catenin[39]
HOXB7↑ in primary or metastatic cancer than chronic gastritis or IMModulation of PI3K/Akt/PTEN axis[41,42]
Associated with advanced TNM stage and undifferentiated type GC
HOXD10↓ in GCPromoter hypermethylation[40]
Induction of IGFBP3
Table 3 Aberrant expression of HOX and non-HOX genes in colorectal cancer
Homeobox geneChangeUnderlying mechanismRef.
CDX1↑ in adenomatous polyp, ↓ in CRCRegulation of cyclin D1 and β-catenin/TCF pathway[55,56,58]
Regulated by miR-215
CDX2↓ in adenoma and CRCLoss of Mucdhl[50-55]
Inversely associated with right side tumor, poorly differentiated type, advanced stage, poor prognosis, CIMP, MMR-deficient tumorInduction of Wnt/β-catenin axis
ALX4↓ in dysplasia and CRCPromoter hypermethylation[59]
PROX1↑ in CRCInduction of β-catenin/TCF axis[60,61]
Associated with advanced stage and lymph node metastasisInhibition of E-cadherin activity
HOXA4, D10↑ in CRCStem cell overpopulation and crypt renewal[63]
HOXA5, A9, A10, C6Proximal colon tumor > distal colon tumorNot presented[64]
HOXB13Distal colon tumor > proximal colon tumorNot presented[64]
HOXB7↑ in CRCActivation of PI3K/Akt and MAPK pathways[67]
Associated with advanced stage, T stage, distant metastasis and poor OS