An essential role of PDCD4 in progression and malignant proliferation of gastrointestinal stromal tumors

Programmed cell death 4 (PDCD4) is a tumor suppressor that can inhibit tumorigenesis by suppressing activator protein (AP)-1 activation and protein translation. Lost or decreased PDCD4 expression has been found in multiple types of human cancers, which was also associated with progression and metastasis of the tumors. However, the status and significance of PDCD4 in gastrointestinal stromal tumors have not been evaluated. In the present study, we examined the PDCD4 expression in a total of 63 gastrointestinal stromal tumor samples at both mRNA and protein levels by RT-PCR, western blot, and immunohistochemistry. We demonstrated that the expression of PDCD4 mRNA was diminished in 68% (17/25) of the tumor samples, and the level of PDCD4 protein appeared to be decreased in 66.7% (42/63) of the samples, as compared to adjacent normal gastrointestinal tissues, which expressed high levels of PDCD4 mRNA and protein. In addition, altered expression of PDCD4 was associated with clinicopathological parameters including risk group, tumor size, and mitosis. Moreover, PDCD4 expression had a negative correlation with the Ki-67 labeling index (r = -0.6059, P < 0.0001). All these results suggest that downregulation of PDCD4 expression may have an essential role in the progression and malignant proliferation of human gastrointestinal stromal tumors.