Role of the TGFbeta/PDCD4/AP-1 Signaling Pathway in Nasopharyngeal Carcinoma and Its Relationship to Prognosis.

BACKGROUND: The objective of the present study was to evaluate the role of the TGFbeta/PDCD4/AP-1 pathway in nasopharyngeal carcinoma (NPC) and its relationship to NPC prognosis. METHODS: NPC tissues collected from 66 NPC patients were compared to 17 nasopharyngeal mucosa biopsy specimens collected as normal tissues. Immunohistochemical staining was performed to assess expression of transforming growth factor-beta receptor I (TGFbetaRI), programmed cell death 4 (PDCD4) and activator protein-1 (AP-1). The Kaplan-Meier method was applied to evaluate NPC patient overall survival (OS) and progression-free-survival (PFS). Cox regression analysis was used to estimate independent prognostic factors for NPC. The human NPC cell line CNE2 was selected and treated with SB431542, an inhibitor of TGFbetaRI; expression of TGFbetaRI and PDCD4 in CNE2 cells was determined by western blotting. NPC tissues showed higher expression of TGFbetaRI and AP-1 but lower expression of PDCD4 than normal tissues (all P < 0.05). RESULTS: The results of Kaplan-Meier analysis showed that TGFbetaRI-positive patients and AP-1-positive patients had shorter OS and PFS than TGFbetaRI-negative patients and AP-1-negative patients; additionally, PDCD4-positive patients had higher OS and PFS than PDCD4-negative patients. Cox regression analysis revealed that advanced tumor stage, overexpression of TGFbetaRI and AP-1, and low expression of PDCD4 were unfavorable factors influencing OS and PFS in NPC patients. Compared with the control group, expression of TGFbetaRI decreased and that of PDCD4 increased significantly in CNE2 cells treated with the inhibitor (all P < 0.05). These findings indicate that the TGFbeta/PDCD4/AP-1 pathway may be associated with NPC development and progression. CONCLUSION: High expression of TGFbetaRI and AP-1 and low expression of PDCD4 may be unfavorable prognostic factors for NPC.