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Genetic variants of CTLA4 are associated with clinical outcome of patients with multiple myeloma.

ABSTRACT: Immune dysfunction in patients with multiple myeloma (MM) affects both the innate and adaptive immune system. Molecules involved in the immune checkpoint pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of these molecules in predicting the kinetics of progression of MM. We retrospectively analysed polymorphisms of CTLA4 (rs231775 and rs733618), BTLA (rs9288953), CD28 (rs3116496), PD-1 (rs36084323 and rs11568821) and LAG-3 (rs870849) genes in 239 patients with newly diagnosed MM. Patients with a CTLA4 rs231775 AA/AG genotype showed a median progression-free survival (PFS) significantly lower than those with GG genotype (32.3 months versus 96.8 months respectively; p: 0.008). The 5-year PFS rate was 25% for patients with grouped AA and AG genotype vs 55.4% for patients with GG genotype. Multivariate analysis confirmed the CTLA4 rs231775 genotype as an independent risk factor for PFS (Hazard Ratio (HR): 2.05; 95% CI: 1.0-6.2; p: 0.047). Our results suggest that the CTLA4 genotype may identify patients with earlier progression of MM. This polymorphism could potentially be used as a prognostic biomarker.

SUBMITTER: Gonzalez-Montes Y

PROVIDER: S-EPMC10143497 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Genetic variants of CTLA4 are associated with clinical outcome of patients with multiple myeloma.

Gonzalez-Montes Yolanda Y Rodriguez-Romanos Rocío R Villavicencio Alicia A Osca-Gelis Gemma G González-Bártulos Marta M Llopis Francesca F Clapes Victòria V Oriol Albert A Sureda Anna A Escoda Lourdes L Sarrà Josep J Garzó Ana A Lloveras Natàlia N Díez Isabel I Granada Isabel I Gallardo David D

Frontiers in immunology 20230412

Immune dysfunction in patients with multiple myeloma (MM) affects both the innate and adaptive immune system. Molecules involved in the immune checkpoint pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of these molecules in predicting the kinetics of progression of MM. We retrospectively analysed polymorphisms of CTLA4 (rs231775 and rs733618), BTLA (rs9288953), CD28 (rs3116496), PD- ...[more]

PMID: 37122695

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Project description:MicroRNAs are small RNA species that regulate gene expression post-transcriptionally and are aberrantly expressed in many cancers including lymphoma. However, the role of microRNAs in the pathogenesis of multiple myeloma (MM) is poorly understood. We therefore elucidated the complete miRNome of purified tumor (CD138+) cells from 33 patients with MM, 5 patients with monoclonal gammopathy of undetermined significance (MGUS) and 9 disease controls. Unsupervised cluster analysis revealed that MM samples have a distinct microRNA expression profile. The majority of microRNAs aberrantly expressed in MM (109/129) were up-regulated. A comparison of these microRNAs with those aberrantly expressed in other B-cell and T-cell lymphomas revealed a surprising degree of similarity (~40%) suggesting the existence of a common lymphoma microRNA signature. We identified 39 microRNAs associated with the pre-malignant condition MGUS. Twenty-three (59%) of these were also aberrantly expressed in MM suggesting common microRNA expression events in MM progression. MM is characterized by multiple chromosomal abnormalities of varying prognostic significance. We identified specific microRNA signatures associated with the most common IgH translocations (t(4;14) and t(11;14)) and del(13q). Expression levels of these microRNAs were distinct between the genetic subtypes (by cluster analysis) and correctly predicted these abnormalities in >85% of cases using the support vector machine algorithm. Additionally, we identified microRNAs associated with light chain only myeloma, as well as IgG and IgA-type MM. Finally, we identified 32 microRNAs associated with event-free survival (EFS) in MM, ten of which were significant by univariate (logrank) survival analysis. In summary, this work has identified aberrantly expressed microRNAs associated with the diagnosis, pathogenesis and prognosis of MM, data which will prove an invaluable resource for understanding the role of microRNAs in this devastating disease. Plasma cells (CD138+) cells were purified from bone marrow samples of 33 patients with MM, 5 patients with monoclonal gammopathy of undetermined significance (MGUS) and 9 disease controls.

Dataset Information

Genetic variants of CTLA4 are associated with clinical outcome of patients with multiple myeloma.

Publications

Genetic variants of CTLA4 are associated with clinical outcome of patients with multiple myeloma.

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