Prognostic significance of PDCD4 expression and association with microRNA-21 in each Dukes' stage of colorectal cancer patients

Abstract

Down-regulation of the novel tumor suppressor gene programmed cell death 4 (PDCD4) was demonstrated in several types of cancer and regulation by micro-RNA is gaining attention. However, the clinical significance of the PDCD4 gene in colorectal cancer (CRC) patients still remains unclear. In particular, the significance of PDCD4 mRNA expression in each tumor stage has not been reported. In this study, we evaluated the prognostic value of PDCD4 expression in each Dukes' stage of CRC patients. Furthermore, relationships between the PDCD4 mRNA and microRNA-21 (miR-21) were evaluated. Tumor tissues and normal adjacent tumor tissues from 326 patients with CRC (Dukes' stage A, 44 cases; Dukes' B, 118 cases; Dukes' C, 100 cases; Dukes' D, 64 cases) were examined. The PDCD4 mRNA was investigated by the quantitative real-time RT-PCR method and miR-21 was examined by TaqMan microRNA assays. The overall survival rates (OS) and disease-free survival rates (DFS) of low PDCD4 patients were significantly worse than those of patients with high expression. In analysis of each tumor stage, OS and DFS of patients with low PDCD4 levels were significantly worse than those with high PDCD4 levels in Dukes' stage B and C. In Dukes' stage D, patients with low PDCD4 expression showed a significant worse OS compared to those of patients with high PDCD4 expression. In contrast, no significant differences were seen between these groups in patients with Dukes' stage A. PDCD4 expression in CRC tissues was an independent prognostic factor in Dukes' stage B, C and D. Significant inverse correlations were demonstrated between PDCD4 and miR-21. The reduced PDCD4 mRNA expression is associated with poor prognosis in CRC patients with Dukes' stage B, C and D. Furthermore, PDCD4 mRNA levels were negatively regulated by miR-21in each tumor stage of CRC.