Abstract

Background and purpose: Radioresistance is one of the main obstacles limiting the therapeutic efficacy of chemoradiotherapy (CRT) and favorable patient prognoses, and the molecular mechanisms underlying this type of resistance remain unclear. The purpose of this study was to identify characteristic genes involved in chemoradiotherapy resistance in nasopharyngeal carcinoma (NPC). Materials and methods: Clinicopathological data of 185 patients with NPC treated at Nanfang Hospital of Southern Medical University between January 2013 and December 2014 were retrospectively analyzed. SPSS statistical software was used to analyze the clinicopathological data related to radiotherapy efficacy. Three patients who achieved complete remission and three with disease progression after CRT were selected. Differentially expressed genes (DEGs) were screened via mRNA microarray analysis of primary diagnostic endoscopy specimens. Results: The peripheral blood leukocyte count, platelet count and EBV-DNA copy number in NPC patients who were resistant to radiotherapy were higher than those in NPC patients who were sensitive to radiotherapy. The RobustRankAggreg (RRA) analysis method identified 392 DEGs, and the 66 most closely related genes among the DEGs were identified from the PPI network. Conclusion: The results of this study indicate that screening for DEGs and pathways in NPC using integrated in silico analyses can help identify a series of genetic and clinical signatures for NPC patients treated with neoadjuvant chemotherapy followed by concurrent chemoradiotherapy. Funding Statement: This work was supported by the Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education (LC2019ZD008); the Clinical Research Startup Program of Nanfang Hospital (2018CR021);the National Natural Science Foundation of China (Grant Nos. 81602685 and 81672992); the Science and Technology Projects in Guangdong Province (Grant Nos. 2018-1201-SF-0019 ); the Health & Medical Collaborative Innovation Project of Guangzhou City, China (201803040003); and the Natural Science Foundation of Guangdong Province (Grant No. 2017A030313486); the Natural Science Foundation of Fujian Province (Grant No. 2017J01245). Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The protocol was approved by the ethics committee of Nanfang Hospital and implemented in accordance with the principles of the Declaration of Helsinki. All participants provided informed consent.

Highlights

  • Nasopharyngeal carcinoma (NPC) is a highly malignant tumor originating from the epithelium; this disease shows a specific ethnic and geographical distribution [1]

  • The aim of this study is to explore the relevant clinical factors or sensitivity predictors of chemoradiotherapy, which will help guide the selection of individualized treatment options for nasopharyngeal carcinoma (NPC) patients, improve the curative effect, and avoid ineffective or excessive treatment

  • The peripheral blood leukocyte count, platelet count, and EBV-DNA copy number were higher in patients with NPC who were resistant to radiotherapy than in those who were sensitive to radiotherapy

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Summary

Introduction

Nasopharyngeal carcinoma (NPC) is a highly malignant tumor originating from the epithelium; this disease shows a specific ethnic and geographical distribution [1]. Improvements in treatment methods and implementation of comprehensive treatment strategies have substantially increased the 5-year survival rate of early-stage NPC patients to approximately. Local control of NPC has improved significantly due to advances in radiotherapy and comprehensive treatments, some patients do not benefit from radiotherapy due to the radiation resistance caused by local recurrence and distant metastasis [7]. The purpose of this study was to identify characteristic genes involved in chemoradiotherapy resistance in nasopharyngeal carcinoma (NPC). Clinicopathological data of 185 patients with NPC treated at Nanfang Hospital of Southern Medical University between January 2013 and December 2014 were retrospectively analyzed. The results of this study indicate that screening for DEGs and pathways in NPC using integrated in silico analyses can help identify a series of genetic and clinical signatures for NPC patients treated with neoadjuvant chemotherapy followed by concurrent chemoradiotherapy

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