Ouyang Zhou, Zeng Ruolan, Wang Song, Wu Xiaoying, Li Yajun, He Yizi, Wang Caiqin, Xia Chen, Ou Qiuxiang, Bao Hua, Yang Wei, Xiao Ling, Zhou Hui
Department of Lymphoma and Hematology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, Changsha, 410013, Hunan, China.
Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, 210032, Jiangsu, China.
Cancer Cell Int. 2025 May 3;25(1):172. doi: 10.1186/s12935-025-03789-9.
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.
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.
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.
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.
套细胞淋巴瘤（MCL）是B细胞非霍奇金淋巴瘤的一种侵袭性亚型。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索。
本研究纳入了34例接受一线化疗免疫治疗的MCL患者。我们评估了血浆ctDNA检测肿瘤特异性基因改变的能力，并探讨了其作为MCL治疗反应和预后的非侵入性生物标志物的潜力。
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）以及BCR和TCR信号通路改变（P = 0.004）和PI3K通路改变（P = 0.008）在母细胞样亚型中富集。ATM突变（P = 0.041）在MIPI低的患者中更常见，而表观遗传染色质重塑通路改变（P = 0.028）在MIPI高的患者中更常见。血浆ctDNA检测结构变异的敏感性较高（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方面表现出中度至高度一致性。治疗前ctDNA水平在预测临床疗效方面具有较高的特异性，但敏感性欠佳，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）显著相关。与较短PFS相关的基于ctDNA的其他遗传特征包括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阳性的ctDNA表明分子复发和预后不良，而检测不到ctDNA则定义了一部分生存结果良好的患者。
本研究确定血浆ctDNA是一种有前景的生物标志物，可无创捕获与MCL治疗反应和生存结果相关的肿瘤衍生基因变异，突出了ctDNA在诊断、复发预测和监测中的临床价值。
