LRP5 polymorphism-A potential predictor of the clinical outcome in advanced gastric cancer patients treated with EOF regimen

Purpose:Wntpathwayscontrolkeybiologicalprocessesthatpotentiallyimpactontumorprogressionandpatientsurvival.Thepresentstudyanalyzedthepolymorphismoflipoprotein-relatedreceptor5(LRP5)(genewithkeyfunctionsinWntsignaling)anditsimpactontheresponsetochemotherapyandsurvivalofpatientswithadvancedgastriccancer(AGC).Methods:Atotalof107consecutivepatientswithAGCtreatedwithfirst-linechemotherapyofEOFregimenwereenrolledinthepresentretrospectivestudy.Theassociationbetweensinglenucleotidepolymorphism(SNP)ofrs3736228inLRP5andtheclinicaloutcomesofthepatientswasstudied.Results:TheCCgenotypeofrs3736228wassignificantlycorrelatedwithahigherdiseasecontrolratewhencomparedtotheCTandTTgenotypes(89.3%and61.8%,respectively,P<0.001).Aunivariatesurvivalanalysisalsoshowedthattheprogressionfreesurvival(PFS)andoverallsurvival(OS)forthepatientswiththeTCandTTgenotypesofrs3736228wereworsethanforthepatientswiththeCCgenotype(PFS:3.3and6.7months,respectively,HR=0.454,P<0.001;OS:8.1monthsand18.8months,respectively,HR=3.056,P<0.001).AmultivariateCoxmodelincorporatesrs3736228andclinicalfeatures,alsoidentifiedrs3736228wassignificantlyassociatedwiththePFSandOS.Conclusions:OurresultsfirstlyhighlighttheimportanceofLRP5geneofWntpathwayinthetreatmentofAGCandidentifypolymorphismofrs3736228asindependentpredictorofdiseasecontrolrate,PFSandOSinAGCpatientstreatedwithfirst-linechemotherapyofEOFregimenintheChineseHanpopulation.