Background:The nasopharyngeal brush sampling can effectively collect samples from the nasopharynx.The blind brush sampling does not require the guidance of endoscopy,which is favorable for implementation and dissemina...Background:The nasopharyngeal brush sampling can effectively collect samples from the nasopharynx.The blind brush sampling does not require the guidance of endoscopy,which is favorable for implementation and dissemination in the community.This study explored methylation markers for nasopharyngeal carcinoma(NPC)at both Epstein-Barr virus(EBV)and its host genome levels,aiming to construct a blind brushing diagnostic method.Methods:EBV DNA capture and methylation sequencing and GEO Illumina 450K methylation array data were used respectively for the discovery of EBV and host methylation markers.The diagnostic method was built in training cohort(n=347)and validated in an independent validation cohort(n=155).Results:A total of 1 EBV methylation marker(BILF2)and 6 host methylation markers(ITGA4,IMPA2,ITPKB,PI9,AMIGO2,and VAV3)were identified.Both EBV and host methylation markers were almost exclusively detected in NPC samples,with negligible detection in control samples.In validation cohort,the diagnostic method that included only the EBV BILF2 marker showed a sensitivity and specificity of 80.22%and 98.44%,respectively.When combining the EBV-derived marker BILF2 with the host-derived marker IMPA2,the diagnostic method's sensitivity increased to 84.62%,while the specificity remained unchanged(IDI=4.4%,P=0.0419).Conclusion:Overall,the blind nasopharyngeal brushing diagnostic method,combining EBV and host methylation markers,showed great potential in NPC detection and could promote its application in nonclinical screening of NPC.展开更多
基金supported by the National Key Research and Development Program of China(grant number 2021YFC2500400)the National Natural Science Foundation of China(grant number 81802708)+2 种基金the Key Area Research and Development Program of Guangdong Province,China(grant number 2019B110233004)the Science and Technology Planning Project of Guangdong Province,China(grant number 2019B030316031)Fundamental Research Funds for the Central Universities,Sun Yat-sen University(grant number 24pnpy289-84000-31610022).
文摘Background:The nasopharyngeal brush sampling can effectively collect samples from the nasopharynx.The blind brush sampling does not require the guidance of endoscopy,which is favorable for implementation and dissemination in the community.This study explored methylation markers for nasopharyngeal carcinoma(NPC)at both Epstein-Barr virus(EBV)and its host genome levels,aiming to construct a blind brushing diagnostic method.Methods:EBV DNA capture and methylation sequencing and GEO Illumina 450K methylation array data were used respectively for the discovery of EBV and host methylation markers.The diagnostic method was built in training cohort(n=347)and validated in an independent validation cohort(n=155).Results:A total of 1 EBV methylation marker(BILF2)and 6 host methylation markers(ITGA4,IMPA2,ITPKB,PI9,AMIGO2,and VAV3)were identified.Both EBV and host methylation markers were almost exclusively detected in NPC samples,with negligible detection in control samples.In validation cohort,the diagnostic method that included only the EBV BILF2 marker showed a sensitivity and specificity of 80.22%and 98.44%,respectively.When combining the EBV-derived marker BILF2 with the host-derived marker IMPA2,the diagnostic method's sensitivity increased to 84.62%,while the specificity remained unchanged(IDI=4.4%,P=0.0419).Conclusion:Overall,the blind nasopharyngeal brushing diagnostic method,combining EBV and host methylation markers,showed great potential in NPC detection and could promote its application in nonclinical screening of NPC.
