The Molecular Characteristics And Differences Of Local Invasion And Distant Metastasis Of Nasopharyngeal Carcinoma Were Explored By Next-generation Sequencing Technology

Objective:Explore the correlation between the occurrence and development of nasopharyngeal carcinoma related mutation genes and clinical features.Looking for biomarkers that predict the occurrence and development of nasopharyngeal carcinoma will lay the foundation for the next step in exploring new therapeutic targets for nasopharyngeal carcinoma.In this study,next-generation sequencing technology was used to perform Whole Exome Sequencing(WES)in 40 patients with nasopharyngeal carcinoma to search for NPC-related mutations,simultaneously analyze the genetic differences of different types of nasopharyngeal carcinoma(upward and downward nasopharyngeal carcinoma);objective to clarify the correlation between the mutant gene and the local invasion of nasopharyngeal carcinoma and regional lymph node metastasis,explore the possibility of establishing a new molecular classification system for nasopharyngeal carcinoma,and provide new ideas for the clinical diagnosis and treatment of nasopharyngeal carcinoma.Methods:A collection of 40 cases of nasopharyngeal carcinoma(group G1: 20 cases of ascending nasopharyngeal carcinoma,G2: 20 cases of descending nasopharyngeal carcinoma)diagnosed in the Oncology Department of Guizhou Provincial People's Hospital from January 2014 to December 2018 Clinical data,through imaging analysis of the difference between ascending nasopharyngeal carcinoma and descending nasopharyngeal carcinoma,from the nasal cavity,posterior pharynx,parapharyngeal space,carotid sheath area,pterygopalatine fossa,maxillary sinus,ethmoid sinus,orbit,intracranial The cavernous sinus,posterior pharynx,and cervical lymph nodes were analyzed for metastasis;and samples of nasopharyngeal cancer tissue and 10 normal nasopharyngeal tissue samples were collected,and DNA was extracted to prepare a library,which was performed on the Illumina sequencing platform.Genomic sequencing,followed by bioinformatics analysis,screened out related high-frequency mutation genes,and analyzed the correlation between the mutation genes and the occurrence,development,invasion and metastasis of nasopharyngeal carcinoma.Results:1.Through imaging analysis,it is found that there are significant differences in imaging characteristics between the G1 group and the G2 group: the nasopharynx in the G1 group is severely damaged,invading the skull base and cranial nerves,but there are few or no regional lymph node metastases.The nasopharynx focal damage in the G2 group was mild,while the cervical lymph nodes frequently metastasized to form huge masses with extracapsular invasion;there was no difference between the cardiopulmonary function and liver and kidney function between the G1 group and the G2 group;2.The high-frequency mutation genes in nasopharyngeal carcinoma tissues are:MUC19,ZNF806,TTN,ANKLE1,CYP2D7,GOLGA6L22,PRR36,PDE4 A,ABO,CACNA1C;3.Through whole exome sequencing,it is found that there are differences between the mutant genes in the G1 group and the G2 group.(The genes with higher mutations in the G1 group are: ANAPC15,ATN1,C11orf30,MALAT1,PTPN6,SUB1;the genes with higher mutations in the G2 group Because: CEP170 B,HNRNPUL1,PAF1,SMG9),and the difference is statistically significant,P<0.05;4.The tumor mutation burden(TMB)of the G1 group and the G2 group was lower,and the tumor heterogeneity(MATH)was higher.There was no statistically significant difference in TMB and MATH between the two groups,P?0.05;5.High-frequency mutation genes are enriched in the ten major signaling pathways related to tumors,namely Hippo signaling pathway,RTK-RAS signaling pathway,Wnt signaling pathway,Notch signaling pathway,PI3 K signaling pathway,6.Myc signaling pathway,Nrf2 signaling pathway,and TGF-? signaling pathway,P53 signaling pathway,Cell-cycle signaling pathway.Conclusions:1.The high-frequency mutation genes in nasopharyngeal carcinoma tissues are:MUC19,ZNF806,TTN,ANKLE1,CYP2D7,GOLGA6L22,PRR36,PDE4 A,ABO,CACNA1 C.These high-frequency mutation genes may become biomarkers for early diagnosis of nasopharyngeal carcinoma;2.Genes with higher mutations in G1 group: ANAPC15,ATN1,C11orf30,MALAT1,PTPN6,and SUB1 may be associated with high local invasiveness of nasopharyngeal carcinoma;genes with higher mutations in G2 group: CEP170 B,HNRNPUL1,PAF1,SMG9 may be associated with nasopharyngeal carcinoma High regional lymph node metastasis is related;3.There is no significant difference in the prospects of immunotherapy between ascending nasopharyngeal carcinoma and descending nasopharyngeal carcinoma;further analysis needs to be combined with clinical objective reality.