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

Abstract

Jing Zhang,1 Lu Zhang,2 Bowen Xie,2 Yumei Duan,3 Ying Wang,4 Liangfang Shen1 1Department of Oncology, Xiangya Hospital, Central South University (CSU), Changsha, 410008, People’s Republic of China; 2Key Laboratory of Molecular Radiation Oncology, Changsha, Hunan Province, 410008, People’s Republic of China; 3Department of Pathology, Xiangya Hospital, CSU, Changsha, 410008, People’s Republic of China; 4Department of Radiology, Xiangya Hospital, CSU, Changsha, 410008, People’s Republic of ChinaCorrespondence: Liangfang ShenDepartment of Oncology, Xiangya Hospital, Central South University (CSU), No. 87 Xiangya Road, Changsha, 410008, Hunan, People’s Republic of ChinaEmail [email protected]: 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.Keywords: PKCα, marker, individualized radiotherapy, nasopharyngeal carcinoma

Keywords

• pkcα
• marker
• individualized radiotherapy
• nasopharyngeal carcinoma