CYP3A5 Polymorphism in Circulating Tumor Cells Confers an Increased Disease-Free Survival in DLBCL Patients Treated with R-CHOP.

IF 2.7 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

OncoTargets and therapy Pub Date : 2025-03-14 eCollection Date: 2025-01-01 DOI:10.2147/OTT.S486400

Rafael Cerón Maldonado, Adolfo Martínez Tovar, Christian Omar Ramos Peñafiel, Adrián De la Cruz Rosas, Anel Irais García Laguna, Iveth Mendoza Salas, Carlos Martínez Murillo, Gilberto Israel Barranco Lampón, Efreen Horacio Montaño Figueroa, Silvia Jiménez-Morales, Irma Olarte Carrillo

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引用次数: 0

Abstract

Purpose: Diffuse Large B-Cell Lymphoma (DLBCL) is a heterogeneous aggressive lymphoid neoplasm. Cases of refractoriness and relapse persist in approximately 40% of patients treated with first-line R-CHOP regimen, thus, the identification of factors associated with disease progression have become a necessity. Diverse polymorphisms in genes encoding proteins involved in the metabolism and elimination of chemotherapeutic drugs have been studied as potential causes of treatment failure. In oncology, liquid biopsies have emerged as a non-invasive method for detecting circulating biomarkers, thereby strengthening both diagnosis and prognosis for patients. Therefore, the purpose of this study was to determine polymorphisms in Circulating Tumor Cells (CTCs) to describe the relevance of liquid biopsy in the clinical outcomes of patients with DLBCL.

Patients and methods: We analyzed 102 liquid biopsies of peripheral blood from DLBCL patients, of which CTCs were isolated by density gradient and CD20 immunomagnetic antibodies. Allelic discrimination assays were performed to analyze ABCB1 C3435T, ABCG2 C421A and CYP3A5 A6986G polymorphisms. Overall survival (OS) and disease-free survival (DFS) analysis were performed using Kaplan-Meier curves and risk analysis was performed using Cox regression.

Results: We found that GG genotype of CYP3A5 A6986G was associated with a longer DFS (68.6% vs 49%, p=0.019) and lower risk of course with adverse event related to disease (progression, relapse and death) (OR 0.374, CI 0.187-0.745, p=0.011). No significant associations were found between ABCB1 C3435T and ABCG2 C421A genotype with the clinical outcome.

Conclusion: In this study, we demonstrated that in CTCs derived from liquid biopsies, the GG genotype in the CYP3A5 A6986G, which is related to the metabolism and elimination of chemotherapy drugs, impacts in longer DFS. These findings confirm the relevance of circulating biomarkers in non-invasive biological samples for strengthening the prognosis of DLBCL.

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循环肿瘤细胞CYP3A5多态性增加了接受R-CHOP治疗的DLBCL患者的无病生存期

目的：弥漫性大b细胞淋巴瘤（DLBCL）是一种异质性侵袭性淋巴样肿瘤。在接受一线R-CHOP方案治疗的患者中，大约40%的患者持续存在难治性和复发，因此，确定与疾病进展相关的因素已成为必要。参与化疗药物代谢和消除的蛋白质编码基因的多种多态性已被研究为治疗失败的潜在原因。在肿瘤学中，液体活检已经成为一种检测循环生物标志物的非侵入性方法，从而加强了患者的诊断和预后。因此，本研究的目的是确定循环肿瘤细胞（CTCs）的多态性，以描述液体活检与DLBCL患者临床结果的相关性。患者和方法：我们分析了102例DLBCL患者外周血液体活检，其中CTCs采用密度梯度和CD20免疫磁性抗体分离。ABCB1 C3435T、ABCG2 C421A和CYP3A5 A6986G等位基因多态性分析。采用Kaplan-Meier曲线分析总生存期（OS）和无病生存期（DFS），采用Cox回归分析风险。结果：我们发现CYP3A5 A6986G的GG基因型与较长的DFS （68.6% vs 49%, p=0.019）和较低的病程不良事件（进展、复发和死亡）风险相关（OR 0.374, CI 0.187-0.745, p=0.011）。ABCB1 C3435T和ABCG2 C421A基因型与临床预后无显著相关性。结论：在本研究中，我们证明了在液体活检的CTCs中，CYP3A5 A6986G中的GG基因型与化疗药物的代谢和消除有关，影响更长的DFS。这些发现证实了非侵入性生物样本中循环生物标志物与加强DLBCL预后的相关性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

OncoTargets and therapy BIOTECHNOLOGY & APPLIED MICROBIOLOGY-ONCOLOGY

CiteScore

9.70

自引率

0.00%

发文量

221

审稿时长

1 months

期刊介绍： OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer. The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype. Specific topics covered by the journal include: -Novel therapeutic targets and innovative agents -Novel therapeutic regimens for improved benefit and/or decreased side effects -Early stage clinical trials Further considerations when submitting to OncoTargets and Therapy: -Studies containing in vivo animal model data will be considered favorably. -Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines. -Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples. -Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Single nucleotide polymorphism (SNP) studies will not be considered.