Dysregulation of miR-126/Crk protein axis predicts poor prognosis in gastric cancer patients.

BACKGROUND

miR-126 functions as a tumor suppressor in gastric cancer (GC) by negatively regulating Crk protein expression post-transcriptionally.

OBJECTIVE

The aim of this study was to investigate the associations of miR-126 and Crk protein expression levels, alone or in combination, with the clinicopathological characteristics and prognosis of GC patients.

METHODS

The expression levels of miR-126 and Crk protein in 338 GC patients were analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. The relationship of miR-126 and Crk protein expression with clinicopathologic characteristics and clinical outcome was evaluated.

RESULTS

Compared with matched adjacent non-tumor tissues, miR-126 was significantly down-regulated while Crk protein was significantly up-regulated in tumor tissues. A reduced miR-126 expression and an elevated Crk protein expression, alone or in combination, statistically correlated with aggressive clinicopathological characteristics, such as larger tumor size, deeper local invasion, more lymph node metastasis, advanced TNM stage, and poorer prognosis. Multivariate analysis showed that combined miR-126-low/Crk protein-high expression was an independent unfavorable prognostic factor of GC.

CONCLUSIONS

These results indicate for the first time that miR-126 down-regulation and Crk protein up-regulation may be synergistically associated with tumor progression in GC and may predict unfavorable prognosis of GC.