Frequent overexpression of PDK1 in primary nasopharyngeal carcinoma is associated with poor prognosis.

OBJECTIVE: Pyruvate dehydrogenase kinase 1 (PDK1) is reported to be up-regulated and play multiple functions in several cancers. Herein, we investigated its roles in primary nasopharyngeal carcinoma. METHODS: Expression of PDK1 protein was examined by immunohistochemical staining in 102 samples of primary nasopharyngeal carcinoma (pNPC) and 31 samples of chronic nasopharyngitis. The relationships of PDK1 expression levels with clinical features and prognosis in NPC patients were analyzed. RESULTS: PDK1 protein expression was significantly greater in pNPC tissues than in the chronic nasopharyngitis tissues (P<0.01). In addition, overexpression of PDK1 was associated with advanced clinical stage (P<0.01), advanced N classification (P=0.024), and distant metastasis (P=0.048). Kaplan-Meier survival analysis demonstrated that patients with higher PDK1 expression had significantly shorter overall survival (P=0.006), disease-free survival (P=0.015), loco-regional relapse-free survival (P=0.008), and distant metastasis-free survival (P=0.017). Furthermore, multi-variate analysis showed that PDK1 expression was an independent prognostic factor in pNPC patients. CONCLUSION: PDK1 is frequently upregulated in pNPC and may serve as a prognostic marker.

Down-regulation of succinate dehydrogenase subunit B and up-regulation of pyruvate dehydrogenase kinase 1 predicts poor prognosis in recurrent nasopharyngeal carcinoma.

Succinate dehydrogenase subunit B (SDHB) and pyruvate dehydrogenase kinase 1 (PDK1) play key roles in the regulation of growth and survival of various cancers. This study aimed to investigate expression of SDHB and PDK1 in recurrent nasopharyngeal carcinoma (rNPC) tissues and analyzed the association of SDHB and PDK1 expression with the clinical significance and potential prognostic implication of rNPC. Immunohistochemistry was performed to determine the expression of SDHB and PDK1 in tissues in primary NPC (pNPC) and rNPC patients. Our results revealed that expression of SDHB in rNPC was significantly lower than that in pNPC, while the expression of PDK1 was higher compared to pNPC. The expression levels of SDHB and PDK1 were associated with T stage, N stage, clinical stage, and metastasis of rNPC. Survival analysis showed that patients with low SDHB expression had a significantly shorter overall survival time than those with high SDHB expression. Patients with high PDK1 expression had a shorter survival time than patients with low PDK1 expression. Multivariate analysis showed that the expression of SDHB and PDK1 was an independent predictor for the survival of patients with rNPC. Our results demonstrated that down-regulation of SDHB and up-regulation of PDK1 may be novel biomarkers for predicting advanced tumor progression and unfavorable prognosis in rNPC patients.