Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 7, 2016; 22(37): 8247-8256
Published online Oct 7, 2016. doi: 10.3748/wjg.v22.i37.8247
Impact of homeobox genes in gastrointestinal cancer
Moon Kyung Joo, Jong-Jae Park, Hoon Jai Chun
Moon Kyung Joo, Jong-Jae Park, Division of Gastroenterology, Department of Internal Medicine, Korea University College of Medicine Guro Hospital, Seoul 08308, South Korea
Hoon Jai Chun, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Institute of Digestive Disease and Nutrition, Korea University College of Medicine, Seoul 02841, South Korea
Author contributions: Joo MK wrote the paper; Park JJ and Chun HJ revised the manuscript for critical intellectual content.
Supported by the Korean College of Helicobacter and Upper Gastrointestinal Research Foundation Grant; and a Korea University Grant, No. K1512661.
Conflict-of-interest statement: None of the authors have potential conflicts (financial, professional, or personal) that are relevant to this publication.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hoon Jai Chun, MD, PhD, AGAF, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Institute of Digestive Disease and Nutrition, Korea University College of Medicine, 126-1, Anam-dong 5 ga, Seongbuk-gu, Seoul 02841, South Korea. drchunhj@chol.com
Telephone: +82-2-9206555 Fax: +82-2-9531943
Received: July 4, 2016
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.

Keywords: Homeobox genes, HOX genes, Caudal-related homeobox transcription factor 2, Gastrointestinal cancers, HOXB7

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.