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

BACKGROUND

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.

METHODS

We assessed expression and biological behavior of OPCML in gastric cancer.

RESULTS

OPCML 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.

CONCLUSION

Down-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.