Published online Oct 7, 2016. doi: 10.3748/wjg.v22.i37.8247
Peer-review started: July 6, 2016
First decision: July 29, 2016
Revised: August 13, 2016
Accepted: August 23, 2016
Article in press: August 23, 2016
Published online: October 7, 2016
Homeobox genes, including HOX and non-HOX genes, have been identified to be expressed aberrantly in solid tumors. In gastrointestinal (GI) cancers, most studies have focused on the function of non-HOX genes including caudal-related homeobox transcription factor 1 (CDX1) and CDX2. CDX2 is a crucial factor in the development of pre-cancerous lesions such as Barrett’s esophagus or intestinal metaplasia in the stomach, and its tumor suppressive role has been investigated in colorectal cancers. Recently, several HOX genes were reported to have specific roles in GI cancers; for example, HOXA13 in esophageal squamous cell cancer and HOXB7 in stomach and colorectal cancers. HOXD10 is upregulated in colorectal cancer while it is silenced epigenetically in gastric cancer. Thus, it is essential to examine the differential expression pattern of various homeobox genes in specific tumor types or cell lineages, and understand their underlying mechanisms. In this review, we summarize the available research on homeobox genes and present their potential value for the prediction of prognosis in GI cancers.
Core tip: Aberrant up- or downregulation of homeobox genes may play pivotal roles in the development and progression of gastrointestinal (GI) cancers. Core research in GI cancers has focused on non-HOX genes including caudal-related homeobox transcription factor 2. However, recent studies have demonstrated significant functions of specific HOX genes, including HOXB7, HOXA13, and HOXD10, in GI cancers. Here, we review the major research data concerning the deregulation of homeobox genes in GI cancers and their underlying mechanisms.