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 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.

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