Changes in tumor-antigen expression profile as human small-cell lung cancers progress

(整期优先)网络出版时间:2015-02-12
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Objective:Ourgrouphaspreviouslyobservedthatinpatientswithsmall-celllungcancers(SCLCs),theexpressionofatumorantigen,gliomabigpotassium(gBK)ionchannel,ishigheratthetimeofdeaththanwhenthecancerisfirsttreatedbysurgicalresection.Thisstudyaimedtodeterminewhetherthisdichotomywascommoninotherpotentiallungtumorantigensbyexaminingthesamepatientsamplesusingourmoreextensiveprofileanalysisoftumor-antigenprecursorprotein(TAPP).WethentestedthehypothesisthattherapeuticinterventionmayinadvertentlycausethisincreasedgBKproduction.Methods:SCLCsamples(eightsurgicalresectionsandthreeautopsysamples)andthreecontrollungswereexaminedbyquantitativereal-timepolymerasechainreactionfor42potentialTAPPsthatrepresentpotentialT-cell-mediatedimmunologicaltargets.Results:Twenty-twoTAPPmRNAsdisplayedthesameprofileasgBK,i.e.,moremRNAswereexpressedatautopsythanintheirsurgicalcounterparts.B-cyclinandmousedoubleminute2,humanhomologofP53-bindingproteinwereelevatedinbothautopsyandsurgicalspecimensabovethenormal-lungcontrols.WhenHTB119cellswereincubatedwithdoxorubicin,gBKwasstronglyinduced,asconfirmedbyintracellularflowcytometrywithagBK-specificantibody.Conclusion:Ourfindingssuggestedthatmoreimmunologicaltargetsbecameavailableasthetumorrespondedtochemotherapyandproceededtowarditsterminalstages.