Updates onSPOPGeneMutationsinProstateCancerand Computational InsightsFromTCGAcBioPortalDatabase

Abstract

Speckle-type poxvirusandzinc*ngerprotein(SPOP)hasemergedasakeyfocusinprostatecancerresearchduetoitscriticalrole in regulatingtheandrogenreceptor(AR)signalingpathway./isreviewaimstocomprehensivelysummarizecurrentknowledge on SPOPgenemutationsinprostatecancer,emphasizingtheirimportanceindiseasecharacterizationandidenti*cationof therapeutic targets.Asystematicliteraturesearchwasconductedacrossmultipledatabases,includingPubMed,WebofScience, Scopus, andGoogleScholar.Inaddition,thisstudyusescomputationalapproachesanddatafromtheTCGAcBioPortaldatabase to explorethelandscapeofSPOPmutationsinprostatecancer.Afterscreening682articlesandfollowingsystematicselection steps, 56high-qualityarticleswereincluded.ComputationalanalysisofTCGAcBioPortaldatarevealedaSPOPmutation prevalence of5%-6%,alongwithsigni*cantalterationsinARsignalingandepigeneticregulation.SPOPmutationsdisrupt substrate recognition,leadingtodysregulationofdownstreampathwayssuchasARsignalingandchromatinremodeling. Notably, SPOP-mutantprostatecancersaremutuallyexclusivewithTMPRSS2-ERGfusionsandenrichedforWntpathway alterations. PatientswithSPOPmutationsdemonstrateprolongedresponsestoandrogendeprivationtherapy(ADT),although concurrent mutationsinTP53orDNArepairgenesnegativelyimpactoutcomes.Whiletheirprognosticsigni*cancecontinuesto evolve, theirimpactontheARpathwayhighlightstheirpotentialastherapeutictargets./eclinicalimplicationsofSPOP mutations aresubstantial,astheyarelinkedtovariationsintreatmentresponseanddiseaseprogression,thusservingasvaluable biomarkers forriskstrati*cationandprognosis.