文章：

用于弥漫性大B细胞淋巴瘤早期检测、治疗反应监测和预后预测的6-tsRNA特征

A 6-tsRNA signature for early detection, treatment response monitoring, and prognosis prediction in diffuse large B cell lymphoma

原文发布日期：2025-04-28

DOI: 10.1038/s41408-025-01267-z

类型: Article

开放获取: 是

英文摘要：

Diffuse large B-cell lymphoma (DLBCL) presents considerable clinical challenges due to its aggressive nature and diverse clinical progression. New molecular biomarkers are urgently needed for outcome prediction. We analyzed blood samples from DLBCL patients and healthy individuals using short, non-coding RNA sequencing. A classifier based on six tsRNAs was developed through random forest and primary component analysis. This classifier, established using Cox proportional hazards modeling with repeated 10-fold cross-validation on an internal cohort of 100 samples analyzed using RT-qPCR, effectively identified high-risk patients with significantly lower overall survival compared to low-risk patients (Hazard ratio: 6.657, 95%CI 2.827-15.68, P = 0.0006). Validation in an external cohort of 160 samples using RT-qPCR confirmed the classifier’s robust performance. High-risk status was strongly associated with disease histological subtype, stage, and International Prognostic Index scores. Integration of the classifier into the IPI model enhanced the precision and consistency of prognostic predictions. A dynamic study revealed that patients experiencing a 1.06-fold decrease after one therapy cycle (early molecular response) exhibited better treatment outcomes and prognosis. Furthermore, the 6-tsRNA signature accurately differentiated healthy individuals from DLBCL (AUC 0.882, 95%CI 0.826-0.939). These findings underscore the potential of the identified 6-tsRNA profile as a biomarker for monitoring treatment effectiveness and predicting DLBCL outcomes.
 

摘要翻译： 

弥漫大B细胞淋巴瘤（DLBCL）因其侵袭性特征及多样的临床进展过程，构成显著的临床挑战，亟需新的分子生物标志物进行预后预测。本研究通过短链非编码RNA测序技术，对DLBCL患者与健康个体的血液样本进行分析。通过随机森林算法和主成分分析，开发出基于六种转运RNA衍生的小型RNA（tsRNA）的分类器。该分类器基于100例内部队列样本的实时定量聚合酶链反应（RT-qPCR）数据，采用Cox比例风险模型结合重复十折交叉验证建立，能有效识别总体生存率显著较低的高危患者（风险比：6.657，95%置信区间2.827-15.68，P=0.0006）。在160例外部队列样本中通过RT-qPCR验证，证实该分类器性能稳健。高危状态与疾病组织学亚型、临床分期及国际预后指数评分显著相关。将该分类器整合至国际预后指数模型后，提升了预后预测的精确度与一致性。动态研究表明，完成一个治疗周期后表达量下降1.06倍（早期分子应答）的患者表现出更好的治疗结果与预后。此外，该六标志物组合能准确区分健康个体与DLBCL患者（曲线下面积0.882，95%置信区间0.826-0.939）。这些发现揭示了该六标志物组合作为监测疗效和预测DLBCL预后的生物标志物的潜力。

原文链接：

A 6-tsRNA signature for early detection, treatment response monitoring, and prognosis prediction in diffuse large B cell lymphoma