CD274 (PD-L1) Polymorphisms as Predictors of Efficacy in First-Line Platinum-Based Chemotherapy for Extensive-Stage Small Cell Lung Cancer
Barba Joaquin, Andrés (Institut de Recerca Sant Pau)
López Vilaró, Laura (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Ferre, Malena (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Martinez-Recio, Sergio (Institut de Recerca Sant Pau)
Majem, Margarita (Institut de Recerca Sant Pau)
Sullivan, Ivana (Institut de Recerca Sant Pau)
Salazar, Juliana (Institut de Recerca Sant Pau)

Date:	2025
Abstract:	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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Extensive-stage small cell lung cancer ; Platinum-based chemotherapy ; Pharmacogenetics ; Biomarker ; CD274 gene ; PD-L1
Published in:	International journal of molecular sciences, Vol. 26 Núm. 9 (April 2025) , ISSN 1422-0067

DOI: 10.3390/ijms26094245
PMID: 40362483

13 p, 2.5 MB

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