Genomic signatures in plasma circulating tumor DNA reveal treatment response and prognostic insights in mantel cell lymphoma.

IF 5.3 2区医学 Q1 ONCOLOGY

Cancer Cell International Pub Date : 2025-05-03 DOI:10.1186/s12935-025-03789-9

Zhou Ouyang, Ruolan Zeng, Song Wang, Xiaoying Wu, Yajun Li, Yizi He, Caiqin Wang, Chen Xia, Qiuxiang Ou, Hua Bao, Wei Yang, Ling Xiao, Hui Zhou

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引用次数: 0

Abstract

Background: Mantle cell lymphoma (MCL) is an aggressive subtype of B-cell non-Hodgkin's lymphoma. The applicability of circulating tumor DNA (ctDNA) for predicting treatment response and prognosis in MCL remains underexplored.

Methods: This study included 34 MCL patients receiving first-line chemoimmunotherapy. We assessed the ability of plasma ctDNA to detect tumor-specific genetic alterations and explored its potential as a noninvasive biomarker for treatment response and prognosis in MCL.

Results: Commonly mutated genes in MCL included CCND1 (93.5%), ATM (48.4%), KMT2D (25.8%), and TP53 (25.8%). Subgroup analysis of tissue samples showed that CDKN2A mutations (P = 0.028), along with alterations in BCR and TCR signaling (P = 0.004) and the PI3K pathway (P = 0.008), were enriched in the blastoid subtype. ATM mutations (P = 0.041) were more prevalent in MIPI-low patients, while epigenetic chromatin remodeling pathway alterations (P = 0.028) were more common in MIPI-high patients. Plasma ctDNA demonstrated high sensitivity for detecting structural variants (96.6%), followed by mutations (71.3%) and copy number variants (30.0%). 75% of patients exhibited moderate-to-high concordance in detecting genomic variants between plasma and tissue samples. Pretreatment ctDNA levels exhibited high specificity in predicting clinical efficacy but had a suboptimal sensitivity of 68.2%. Higher ctDNA levels were significantly associated with shorter progression-free survival (PFS; P = 0.002) and overall survival (OS; P = 0.009). Additional ctDNA-based genetic features associated with shorter PFS included TP53 (P = 0.002), TRAF2 (P = 0.023), and SMARCA4 (P = 0.023) mutations, while TP53 (P = 0.006) and TERT (P = 0.031) mutations predicted shorter OS. Persistent positive ctDNA in post-treatment plasma samples indicated molecular relapse and poor prognosis, whereas undetectable ctDNA defined a subset of patients with favorable survival outcomes.

Conclusions: This study identified plasma ctDNA as a promising biomarker that noninvasively captures tumor-derived genetic variants associated with treatment response and survival outcomes in MCL, highlighting the clinical value of ctDNA for diagnosis, recurrence prediction, and surveillance monitoring.

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血浆循环肿瘤DNA的基因组特征揭示了mantle细胞淋巴瘤的治疗反应和预后见解。

背景：套细胞淋巴瘤（MCL）是b细胞非霍奇金淋巴瘤的侵袭性亚型。循环肿瘤DNA （ctDNA）在预测MCL治疗反应和预后方面的适用性仍未得到充分探讨。方法：本研究纳入34例接受一线化疗免疫治疗的MCL患者。我们评估了血浆ctDNA检测肿瘤特异性遗传改变的能力，并探索了其作为MCL治疗反应和预后的非侵入性生物标志物的潜力。结果：MCL中常见的突变基因包括CCND1（93.5%）、ATM（48.4%）、KMT2D（25.8%）和TP53（25.8%）。组织样本的亚组分析显示，CDKN2A突变（P = 0.028）、BCR和TCR信号通路（P = 0.004）和PI3K通路（P = 0.008）在囊胚亚型中富集。ATM突变（P = 0.041）在mipi低的患者中更为普遍，而表观遗传染色质重塑途径改变（P = 0.028）在mipi高的患者中更为常见。血浆ctDNA检测结构变异的灵敏度较高（96.6%），其次是突变（71.3%）和拷贝数变异（30.0%）。75%的患者在检测血浆和组织样本之间的基因组变异时表现出中度至高度的一致性。预处理ctDNA水平在预测临床疗效方面具有很高的特异性，但灵敏度为68.2%。较高的ctDNA水平与较短的无进展生存期(PFS；P = 0.002)和总生存期(OS；p = 0.009)。与较短PFS相关的其他基于ctdna的遗传特征包括TP53 （P = 0.002）、TRAF2 （P = 0.023）和SMARCA4 （P = 0.023）突变，而TP53 （P = 0.006）和TERT （P = 0.031）突变预测较短的OS。治疗后血浆样本中持续的ctDNA阳性表明分子复发和预后不良，而未检测到ctDNA的患者则具有良好的生存结果。结论：本研究确定血浆ctDNA是一种很有前景的生物标志物，它可以无创地捕获与MCL治疗反应和生存结果相关的肿瘤来源的遗传变异，突出了ctDNA在诊断、复发预测和监测方面的临床价值。

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

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.