Construction Of A Multirisk Gene Regulatory Network For Nasopharyngeal Carcinoma And The Dynamics Of Its Enriched NF-?B Signaling Pathway Mediated By Latent Membrane Protein1 Encoded By Epstein-Barr Virus

Nasopharyngeal carcinoma(NPC)is a type of cancer that occurs in southern China and surrounding areas.Among malignant tumors of human head and neck,the incidence rate of nasopharyngeal cancer ranks the first in China,and it is one of the top ten tumors for national key prevention and control.Nasopharyngeal cancer is caused by a variety of causes,such as EPstein-Barr virus infection and lifestyle.However,the etiology of nasopharyngeal carcinoma is still unclear.The treatment and prognosis of nasopharyngeal carcinoma are related to various factors,including epithelial gene mutation,tumor angiogenesis,cellular immune response and tumorrelated gene mutation.Today,the molecular biology of NASopharyngeal carcinoma is still dominant,such as the interaction of chemical(environmental)factors with the carcinogenesis pathway of NASopharyngeal carcinoma(oncogene and tumor suppressor gene changes).Therefore,it is of great practical significance to construct a gene regulatory network from the molecular level to study the influence of multiple risk factors on the pathogenesis of NASopharyngeal carcinoma.This paper is divided into four chapters.The first chapter introduces the research status and significance of this paper,and summarizes the key work of this paper.In chapter 2,the novel molecular markers of nasopharyngeal carcinoma were studied using the methods of systems biology.The microarray gene expression dataset of nasopharyngeal carcinoma and six risk factors was analyzed based on gene regulatory network analysis method,and the differentially expressed genes shared by the disease and risk factors were identified.Then,the metabolic and signaling pathways related to NASopharyngeal carcinoma were determined by gene aggregation analysis,in which NF-B signaling pathway was the most important in the development of nasopharyngeal carcinoma.Protein subnets and central proteins were identified by protein-protein interaction(PPI)network analysis.Finally,novel possible molecular markers BUB1 B,CDC20,AURKB and PTTG1 for NPC were screened out,and these biomarkers may also contribute to the development of new treatments and post-treatment planning for NPC.In Chapter 3,a confirmed tumor marker LMP1 of nasopharyngeal carcinoma was introduced based on the NF-B signaling pathway screened out in Chapter 2.Based on the NF-?B regulatory network established by previous studies,LMP1 was added into the differential equations as a new state variable.In this paper,the l MP1-NF-B gene regulation system is studied by dynamical system method.The significance of time delay on system oscillation and the influence of key parameters on LMP1-NF-?B gene regulation system are discussed.Epstein-barr virus encoded membrane protein LMP1 can activate the NF-?B nuclear factor pathway and promote the formation of nasopharyngeal carcinoma,and time delay is also important for the development of the disease as a non-negligible factor.The fourth chapter summarizes this paper,summarizes the innovation and limitations of this paper,and puts forward the future research direction and assumptions.