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The role of functional polymorphisms in immune response genes as biomarkers of BCG Immunotherapy outcome in bladder cancer: Establishment of a predictive profile in a Southern Europe population

2014-06-16Journal article Open access
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dc.contributor.authorLima, Luís
dc.contributor.authorOliveira, Daniela
dc.contributor.authorFerreira, José Alexandre
dc.contributor.authorTavares, Ana
dc.contributor.authorCruz, Ricardo
dc.contributor.authorMedeiros, Rui
dc.contributor.authorSantos, Lúcio
dc.date.accessioned2015-01-27T17:58:12Z
dc.date.available2015-01-27T17:58:12Z
dc.date.issued2014-06-16
dc.description.abstractOBJECTIVE: To evaluate the predictive value of genetic polymorphisms in the context of BCG immunotherapy outcome and create a predictive profile that may allow discriminating the risk of recurrence. MATERIAL AND METHODS: In a dataset of 204 patients treated with BCG, we evaluate 42 genetic polymorphisms in 38 genes involved in the BCG mechanism of action, using Sequenom MassARRAY technology. Stepwise multivariate Cox Regression was used for data mining. RESULTS: In agreement with previous studies we observed that gender, age, tumor multiplicity and treatment scheme were associated with BCG failure. Using stepwise multivariate Cox Regression analysis we propose the first predictive profile of BCG immunotherapy outcome and a risk score based on polymorphisms in immune system molecules (SNPs in TNFA-1031T/C (rs1799964), IL2RA rs2104286 T/C, IL17A-197G/A (rs2275913), IL17RA-809A/G (rs4819554), IL18R1 rs3771171 T/C, ICAM1 K469E (rs5498), FASL-844T/C (rs763110) and TRAILR1-397T/G (rs79037040) in association with clinicopathological variables. This risk score allows the categorization of patients into risk groups: patients within the Low Risk group have a 90% chance of successful treatment, whereas patients in the High Risk group present 75% chance of recurrence after BCG treatment. CONCLUSION: We have established the first predictive score of BCG immunotherapy outcome combining clinicopathological characteristics and a panel of genetic polymorphisms. Further studies using an independent cohort are warranted. Moreover, the inclusion of other biomarkers may help to improve the proposed model.por
dc.identifier.doi10.1111/bju.12844
dc.identifier.urihttp://hdl.handle.net/10400.22/5489
dc.language.isoengpor
dc.peerreviewedyespor
dc.subjectBCG immunotherapypor
dc.subjectbladder cancerpor
dc.subjectpolymorphismspor
dc.subjectpredictive profilepor
dc.subjectrisk score of recurrencepor
dc.titleThe role of functional polymorphisms in immune response genes as biomarkers of BCG Immunotherapy outcome in bladder cancer: Establishment of a predictive profile in a Southern Europe populationpor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlacePortugalpor
oaire.citation.titleBJU Internationalpor
person.familyNameOliveira Lima
person.givenNameLuís Carlos
person.identifier.ciencia-id9F16-0E29-D9FC
person.identifier.orcid0000-0001-8152-9237
person.identifier.scopus-author-id23501978900
rcaap.rightsopenAccesspor
rcaap.typearticlepor
relation.isAuthorOfPublicationc6b00c1f-f4c9-4f4f-b291-17cf30b1e1f8
relation.isAuthorOfPublication.latestForDiscoveryc6b00c1f-f4c9-4f4f-b291-17cf30b1e1f8

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