Published online May 7, 2018. doi: 10.3748/wjg.v24.i17.1881
Peer-review started: March 12, 2018
First decision: March 29, 2018
Revised: April 6, 2018
Accepted: April 9, 2018
Article in press: April 9, 2018
Published online: May 7, 2018
Processing time: 56 Days and 4.7 Hours
Olfactomedin-4 (OLFM4, GW112, hGC-1) is a glycoprotein belonging to the olfactomedin family. The expression of OLFM4 is strong in the small intestine, colon and prostate, and moderate in the stomach and bone marrow. Previous studies have revealed that OLFM4 is closely associated with many digestive diseases. Up-regulation of OLFM4 has been detected in the Helicobacter pylori (H. pylori)-infected gastric mucosa, inflammatory bowel disease tissue and gastrointestinal malignancies, including gastric cancer, colorectal cancer, pancreatic cancer and gallbladder cancer. Down-regulation of OLFM4 has also been detected in some cases, such as in poorly differentiated, advanced-stage and metastatic tumors. Studies using OLFM4-deficient mouse models have revealed that OLFM4 acts as a negative regulator of H. pylori-specific immune responses and plays an important role in mucosal defense in inflammatory bowel disease. Patients with OLFM4-positive gastric cancer or colorectal cancer have a better survival rate than OLFM4-negative patients. However, the prognosis is worse in pancreatic cancer patients with high levels of expression of OLFM4. The NF-κB, Notch and Wnt signaling pathways are involved in the regulation of OLFM4 expression in digestive diseases, and its role in pathogenesis is associated with anti-inflammation, apoptosis, cell adhesion and proliferation. OLFM4 may serve as a potential specific diagnostic marker and a therapeutic target in digestive diseases. Further studies are required to explore the clinical value of OLFM4.
Core tip: This review is based on the currently available literature about olfactomedin-4 (OLFM4) and is intended to reveal the link between OLFM4 and digestive diseases, including Helicobacter pylori infection, inflammatory bowel disease and gastrointestinal malignancies. The data on the expression, function and regulatory pathways of OLFM4 in digestive diseases are summarized. The potential clinical value of OLFM4 in digestive diseases is also discussed.