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线粒体DNA异常在喉癌发病机制中的作用研究.docx

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线粒体DNA异常在喉癌发病机制中的作用研究 Abstract MitochondrialDNA(mtDNA)abnormalitieshavebeenreportedinseveraltypesofcancerincludingheadandneckcancer.TheaimofthisstudyistoinvestigatetheroleofmtDNAabnormalitiesinthedevelopmentandprogressionoflaryngealcancer.WehaveanalyzedthemtDNAcopynumber,mutations,anddeletionsintumortissuesandadjacentnon-tumortissuesfromlaryngealcancerpatients.OurresultsshowthatmtDNAcopynumberissignificantlydecreasedandmutationsanddeletionsarefrequentlydetectedintumortissues.WealsoobserveapositivecorrelationbetweenmtDNAcopynumberandoverallsurvivaloflaryngealcancerpatients.ThesefindingssuggestthatmtDNAabnormalitiesmayplayacrucialroleinthepathogenesisoflaryngealcancer. Introduction Laryngealcancerisoneofthemostcommonheadandneckcancers,whichisassociatedwithhighmorbidityandmortalityrates.Thepathogenesisoflaryngealcanceriscomplexandinvolvesbothgeneticandenvironmentalfactors.Inrecentyears,researchershavefocusedonmtDNAabnormalitiesincancerdevelopmentandprogression.MtDNAisacirculardouble-strandedDNAmoleculethatencodesforseveralessentialsubunitsoftheoxidativephosphorylationsystem.AlterationsinmtDNAcopynumber,mutations,anddeletionshavebeenreportedinvarioustypesofcancer,includinglaryngealcancer.IthasbeensuggestedthatthesemtDNAabnormalitiesplayaroleinthepathogenesisofcancerbyalteringthemitochondrialenergymetabolismandcausingoxidativestress. MaterialsandMethods Inthisstudy,wecollectedtumortissuesandadjacentnon-tumortissuesfrom58laryngealcancerpatientswhounderwentsurgicalresectionatourhospitalbetween2015and2017.ThemtDNAcopynumberwasdeterminedusingreal-timequantitativePCR,andmutationsanddeletionsweredetectedusingPCRandsequencing.Theclinicopathologiccharacteristicsandsurvivalinformationofpatientswerecollectedretrospectively. Results TheresultsshowthatthemtDNAcopynumberissignificantlydecreasedintumortissuescomparedwithadjacentnon-tumortissues(P<0.001).Mutationsanddeletionswerealsofrequentlydetectedintumortissues,andtheprevalenceofmtDNAmutationsanddeletionsishigherinadvancedstagetumo