CD274 (PD-L1) Polymorphisms as Predictors of Efficacy in First-Line Platinum-Based Chemotherapy for Extensive-Stage Small Cell Lung Cancer

The cornerstone of first-line treatment in extensive-stage small cell lung cancer (ES-SCLC) is platinum- and etoposide-based chemotherapy. Platinum compounds could immunomodulate the tumor microenvironment in addition to their cytotoxic effect. Genetic variation in immune checkpoint (IC) pathways ma...

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Authors: Barba, A, López-Vilaró, L, Ferre, M, Martinez-Recio, S, Majem, M, Sullivan, I, Salazar, J
Format: article
Status:Published version
Publication Date:2025
Country:España
Institution:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repository:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p19567
Online Access:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19567
Access Level:Open access
Keyword:extensive-stage small cell lung cancer
platinum-based chemotherapy
pharmacogenetics
biomarker
<italic>CD274</italic> gene
PD-L1
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spelling CD274 (PD-L1) Polymorphisms as Predictors of Efficacy in First-Line Platinum-Based Chemotherapy for Extensive-Stage Small Cell Lung CancerBarba, ALópez-Vilaró, LFerre, MMartinez-Recio, SMajem, MSullivan, ISalazar, Jextensive-stage small cell lung cancerplatinum-based chemotherapypharmacogeneticsbiomarker<italic>CD274</italic> genePD-L1The cornerstone of first-line treatment in extensive-stage small cell lung cancer (ES-SCLC) is platinum- and etoposide-based chemotherapy. Platinum compounds could immunomodulate the tumor microenvironment in addition to their cytotoxic effect. Genetic variation in immune checkpoint (IC) pathways may predict chemotherapy efficacy. Polymorphisms in the IC genes were determined, and their association with survival was analyzed in 78 patients with ES-SCLC treated with chemotherapy. PD-L1 protein expression in tumor tissue was determined. Three variants in CD274 were associated with better median progression-free survival (mPFS): rs2297136 (hazard ratio [HR] 0.52, 95% CI 0.29-0.93; p = 0.03), rs2282055 (HR 0.23, 95% CI 0.09-0.64; p = 0.005), and rs822336 (HR 0.41, 95% CI 0.23-0.73; p = 0.002). CTLA4 rs231775 was also associated with mPFS (HR 0.30, 95% CI 0.14-0.63; p = 0.002). The variants CD274 rs2297136 and CD274 rs822336 were associated with platinum sensitivity (odds ratio [OR] 0.13, 95% CI 0.02-0.70; p = 0.02, and OR 0.08, 95% CI 0.01-0.46; p = 0.005, respectively). CD274 rs2297136 was also associated with better overall survival (p = 0.02), but not after adjustment for covariates. No association was found between CD274 germline variants and PD-L1 tumor expression. Our results suggest that CD274 and CTLA4 variants may be predictive biomarkers for platinum plus etoposide treatment in ES-SCLC.MDPI2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19567INTERNATIONAL JOURNAL OF MOLECULAR SCIENCESISSN: 16616596ISSNe: 14220067reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p195672026-06-14T12:41:47Z
dc.title.none.fl_str_mv CD274 (PD-L1) Polymorphisms as Predictors of Efficacy in First-Line Platinum-Based Chemotherapy for Extensive-Stage Small Cell Lung Cancer
title CD274 (PD-L1) Polymorphisms as Predictors of Efficacy in First-Line Platinum-Based Chemotherapy for Extensive-Stage Small Cell Lung Cancer
spellingShingle CD274 (PD-L1) Polymorphisms as Predictors of Efficacy in First-Line Platinum-Based Chemotherapy for Extensive-Stage Small Cell Lung Cancer
Barba, A
extensive-stage small cell lung cancer
platinum-based chemotherapy
pharmacogenetics
biomarker
<italic>CD274</italic> gene
PD-L1
title_short CD274 (PD-L1) Polymorphisms as Predictors of Efficacy in First-Line Platinum-Based Chemotherapy for Extensive-Stage Small Cell Lung Cancer
title_full CD274 (PD-L1) Polymorphisms as Predictors of Efficacy in First-Line Platinum-Based Chemotherapy for Extensive-Stage Small Cell Lung Cancer
title_fullStr CD274 (PD-L1) Polymorphisms as Predictors of Efficacy in First-Line Platinum-Based Chemotherapy for Extensive-Stage Small Cell Lung Cancer
title_full_unstemmed CD274 (PD-L1) Polymorphisms as Predictors of Efficacy in First-Line Platinum-Based Chemotherapy for Extensive-Stage Small Cell Lung Cancer
title_sort CD274 (PD-L1) Polymorphisms as Predictors of Efficacy in First-Line Platinum-Based Chemotherapy for Extensive-Stage Small Cell Lung Cancer
dc.creator.none.fl_str_mv Barba, A
López-Vilaró, L
Ferre, M
Martinez-Recio, S
Majem, M
Sullivan, I
Salazar, J
author Barba, A
author_facet Barba, A
López-Vilaró, L
Ferre, M
Martinez-Recio, S
Majem, M
Sullivan, I
Salazar, J
author_role author
author2 López-Vilaró, L
Ferre, M
Martinez-Recio, S
Majem, M
Sullivan, I
Salazar, J
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv extensive-stage small cell lung cancer
platinum-based chemotherapy
pharmacogenetics
biomarker
<italic>CD274</italic> gene
PD-L1
topic extensive-stage small cell lung cancer
platinum-based chemotherapy
pharmacogenetics
biomarker
<italic>CD274</italic> gene
PD-L1
description The cornerstone of first-line treatment in extensive-stage small cell lung cancer (ES-SCLC) is platinum- and etoposide-based chemotherapy. Platinum compounds could immunomodulate the tumor microenvironment in addition to their cytotoxic effect. Genetic variation in immune checkpoint (IC) pathways may predict chemotherapy efficacy. Polymorphisms in the IC genes were determined, and their association with survival was analyzed in 78 patients with ES-SCLC treated with chemotherapy. PD-L1 protein expression in tumor tissue was determined. Three variants in CD274 were associated with better median progression-free survival (mPFS): rs2297136 (hazard ratio [HR] 0.52, 95% CI 0.29-0.93; p = 0.03), rs2282055 (HR 0.23, 95% CI 0.09-0.64; p = 0.005), and rs822336 (HR 0.41, 95% CI 0.23-0.73; p = 0.002). CTLA4 rs231775 was also associated with mPFS (HR 0.30, 95% CI 0.14-0.63; p = 0.002). The variants CD274 rs2297136 and CD274 rs822336 were associated with platinum sensitivity (odds ratio [OR] 0.13, 95% CI 0.02-0.70; p = 0.02, and OR 0.08, 95% CI 0.01-0.46; p = 0.005, respectively). CD274 rs2297136 was also associated with better overall survival (p = 0.02), but not after adjustment for covariates. No association was found between CD274 germline variants and PD-L1 tumor expression. Our results suggest that CD274 and CTLA4 variants may be predictive biomarkers for platinum plus etoposide treatment in ES-SCLC.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19567
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19567
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN: 16616596
ISSNe: 14220067
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869409356197396480
score 15.811543

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