Down-regulated expression of OPCML predicts an unfavorable prognosis and promotes disease progression in human gastric cancer

Yongfei Wang,Weibin Cai,Jinxia Jiao,Xiangliang Zhang,Huijuan Shi,Ming Li,Longshan Liu,Sanmei Ma,Yang Yang,Xiangbin Xing,Minhu Chen

doi:10.1186/s12885-017-3203-y

Abstract

BackgroundOPCML belongs to the IgLON family of Ig domain–containing GPI-anchored cell adhesion molecules and was recently found to be involved in carcinogenesis, while its role in gastric cancer remains unclear.MethodsWe assessed expression and biological behavior of OPCML in gastric cancer.ResultsOPCML expression was markedly reduced in tumor tissues and cancer cell lines. Decreased OPCML expression had a significant association with unfavorable tumor stage (p = 0.007) and grading (p < 0.001). Furthermore, the results revealed that OPCML was an independent prognostic factor for overall survival in gastric cancer (p = 0.002). In addition, ectopic expression of OPCML in cancer cells significantly inhibited cell viability (p < 0.01) and colony formation (p < 0.001), arrest cell cycle in G0/G1 phase and induced apoptosis, and suppressed tumor formation in nude mice. The alterations of phosphorylation status of AKT and its substrate GSK3β, up-regulation of pro-apoptotic regulators including caspase-3, caspase-9 and PARP, and up-regulation of cell cycle regulator p27, were implicated in the biological activity of OPCML in cancer cells.ConclusionDown-regulated OPCML expression might serve as an independent predictor for unfavorable prognosis of patients, and the biological behavior supports its role as a tumor suppressor in gastric cancer.

Highlights

Opioid binding protein/cell adhesion molecule-like gene (OPCML) belongs to the IgLON family of Ig domain–containing GPI-anchored cell adhesion molecules and was recently found to be involved in carcinogenesis, while its role in gastric cancer remains unclear
We subsequently analyzed the association between OPCML expression and clinicopathological characteristics of gastric cancer patients
The results showed that expressions of both OPCML mRNA and protein were markedly downregulated or lost in all seven gastric cancer cell lines, while it is readily detectable in the normal stomach tissues (Fig. 2a, b)

Summary

Introduction

OPCML belongs to the IgLON family of Ig domain–containing GPI-anchored cell adhesion molecules and was recently found to be involved in carcinogenesis, while its role in gastric cancer remains unclear. The majority of gastric cancer patients are diagnosed at an advanced stage and the limited options are available for the treatment. Studies have shown that the Opioid binding protein/cell adhesion molecule-like gene (OPCML), designated as OBCAM, was initially identified from rat brains and found to possess a specific opioid-binding activity [7]. It was later found to be a member of the IgLON family of GPI-anchored cell adhesion molecules, consisting of protein-protein interaction domains, such as three ‘I’ set Ig domains [8, 9]. Studies show that OPCML is normally expressed in brain and

Methods

Results

Discussion

Conclusion