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dc.contributor.authorFenor de la Maza, MD
dc.contributor.authorChandran, K
dc.contributor.authorRekowski, J
dc.contributor.authorShui, IM
dc.contributor.authorGurel, B
dc.contributor.authorCross, E
dc.contributor.authorCarreira, S
dc.contributor.authorYuan, W
dc.contributor.authorWestaby, D
dc.contributor.authorMiranda, S
dc.contributor.authorFerreira, A
dc.contributor.authorSeed, G
dc.contributor.authorCrespo, M
dc.contributor.authorFigueiredo, I
dc.contributor.authorBertan, C
dc.contributor.authorGil, V
dc.contributor.authorRiisnaes, R
dc.contributor.authorSharp, A
dc.contributor.authorRodrigues, DN
dc.contributor.authorRescigno, P
dc.contributor.authorTunariu, N
dc.contributor.authorLiu, XQ
dc.contributor.authorCristescu, R
dc.contributor.authorSchloss, C
dc.contributor.authorYap, C
dc.contributor.authorde Bono, JS
dc.coverage.spatialNetherlands
dc.date.accessioned2022-06-30T11:23:46Z
dc.date.available2022-06-30T11:23:46Z
dc.date.issued2022-04-28
dc.identifierS2588-9311(22)00060-8
dc.identifier.citationEuropean Urology Oncology, 2022, pp. S2588-9311(22)00060-8 -
dc.identifier.issn2588-9311
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5199
dc.identifier.eissn2588-9311
dc.identifier.eissn2588-9311
dc.description.abstractBACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease in which molecular stratification is needed to improve clinical outcomes. The identification of predictive biomarkers can have a major impact on the care of these patients, but the availability of metastatic tissue samples for research in this setting is limited. OBJECTIVE: To study the prevalence of immune biomarkers of potential clinical utility to immunotherapy in mCRPC and to determine their association with overall survival (OS). DESIGN, SETTING, AND PARTICIPANTS: From 100 patients, mCRPC biopsies were assayed by whole exome sequencing, targeted next-generation sequencing, RNA sequencing, tumor mutational burden, T-cell-inflamed gene expression profile (TcellinfGEP) score (Nanostring), and immunohistochemistry for programmed cell death 1 ligand 1 (PD-L1), ataxia-telangiectasia mutated (ATM), phosphatase and tensin homolog (PTEN), SRY homology box 2 (SOX2), and the presence of neuroendocrine features. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The phi coefficient determined correlations between biomarkers of interest. OS was assessed using Kaplan-Meier curves and adjusted hazard ratios (aHRs) from Cox regression. RESULTS AND LIMITATIONS: PD-L1 and SOX2 protein expression was detected by immunohistochemistry (combined positive score ≥1 and >5% cells, respectively) in 24 (33%) and 27 (27%) mCRPC biopsies, respectively; 23 (26%) mCRPC biopsies had high TcellinfGEP scores (>-0.318). PD-L1 protein expression and TcellinfGEP scores were positively correlated (phi 0.63 [0.45; 0.76]). PD-L1 protein expression (aHR: 1.90 [1.05; 3.45]), high TcellinfGEP score (aHR: 1.86 [1.04; 3.31]), and SOX2 expression (aHR: 2.09 [1.20; 3.64]) were associated with worse OS. CONCLUSIONS: PD-L1, TcellinfGEP score, and SOX2 are prognostic of outcome from the mCRPC setting. If validated, predictive biomarker studies incorporating survival endpoints need to take these findings into consideration. PATIENT SUMMARY: This study presents an analysis of immune biomarkers in biopsies from patients with metastatic prostate cancer. We describe tumor alterations that predict prognosis that can impact future studies.
dc.formatPrint-Electronic
dc.format.extentS2588-9311(22)00060-8 -
dc.languageeng
dc.language.isoeng
dc.publisherELSEVIER
dc.relation.ispartofEuropean Urology Oncology
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCorrelation
dc.subjectOverall survival
dc.subjectPD-L1
dc.subjectSOX2
dc.subjectT-cell–inflamed gene expression profile
dc.titleImmune Biomarkers in Metastatic Castration-resistant Prostate Cancer.
dc.typeJournal Article
dcterms.dateAccepted2022-04-13
dc.date.updated2022-06-30T11:22:15Z
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1016/j.euo.2022.04.004
rioxxterms.licenseref.startdate2022-04-28
rioxxterms.typeJournal Article/Review
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/35491356
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Translational Therapeutics
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/18/19 Starting Cohort
pubs.organisational-group/ICR/Students/PhD and MPhil/20/21 Starting Cohort
pubs.publication-statusPublished online
icr.researchteamCancer Biomarkers
icr.researchteamTranslational Therapeutic
icr.researchteamClin Trials & Stats Unit
icr.researchteamPrCa Targeted Therapy
dc.contributor.icrauthorGurel, Bora
dc.contributor.icrauthorCarreira, Suzanne
dc.contributor.icrauthorWestaby, Daniel
dc.contributor.icrauthorMiranda, Susana
dc.contributor.icrauthorSharp, Adam
dc.contributor.icrauthorRescigno, Pasquale
dc.contributor.icrauthorYap, Christina
dc.contributor.icrauthorDe Bono, Johann


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