PKCα is a Potentially Useful Marker for Planning Individualized Radiotherapy for Nasopharyngeal Carcinoma

PURPOSE: To examine the expression of protein kinase C alpha (PKCα) in nasopharyngeal carcinoma (NPC) and determine its relationship to the radio-sensitivity of NPC in order to evaluate its potential as a molecular marker for the guidance of individualized radiation therapy for NPC. MATERIALS AND METHODS: PKCα expression levels were detected in tumor samples from patients and in NPC cell lines with varying degrees of radio-sensitivity. A survival analysis was performed to analyze the association of PKCα expression with the 5-year overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) in patients. In vitro and in vivo experiments using NPC cell lines were performed to study the effects of down-regulation of PKCα by short hairpin RNA treatment on the radio-sensitivity of NPC. RESULTS: PKCα expression was up-regulated in the well-differentiated NPC tissues of patients and in the more radio-resistant NPC cell lines. Moreover, high PKCα expression was associated with a worse 5-year PFS and LRFS of patients. shRNA-mediated knockdown of PKCα led to an increase in the sensitivity of NPC cells to radiation therapy, both in vitro as cultured cells and in vivo as tumor xenografts. CONCLUSION: The elevated expression of PKCα in NPC and its association with patient PFS indicates that PKCα is a potential molecular marker for guiding precision radiotherapy in NPC patients. Also, the increased radiosensitivity of NPC cells after loss of PKCα identifies PKCα as a promising therapeutic target for enhancing the radio-sensitivity of NPC.