整合多组学特征能够实现弥漫性大B细胞淋巴瘤的非侵入性早期诊断和治疗反应预测。

Integrating multi-omics features enables non-invasive early diagnosis and treatment response prediction of diffuse large B-cell lymphoma.

作者信息

Zhang Weilong, Ye Bangquan, Song Yang, Yang Ping, Si Wenzhe, Jing Hairong, Yang Fan, Yuan Dan, Wu Zhihong, Lyu Jiahao, Peng Kang, Zhang Xu, Wang Lingli, Li Yan, Liu Yan, Wu Chaoling, Hao Xiaoyu, Zhang Yuqi, Qi Wenxin, Wang Jing, Dong Fei, Zhao Zijian, Jing Hongmei, Li Yanzhao

机构信息

Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, Beijing, China.

BOE Technology Group Co., Ltd, Beijing, China.

出版信息

Clin Transl Med. 2025 Jan;15(1):e70174. doi: 10.1002/ctm2.70174.

DOI:10.1002/ctm2.70174

PMID:39776291

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11705727/

Abstract

BACKGROUND

Multi-omics features of cell-free DNA (cfDNA) can effectively improve the performance of non-invasive early diagnosis and prognosis of cancer. However, multimodal characterization of cfDNA remains technically challenging.

METHODS

We developed a comprehensive multi-omics solution (COMOS) to specifically obtain an extensive fragmentomics landscape, presented by breakpoint characteristics of nucleosomes, CpG islands, DNase clusters and enhancers, besides typical methylation, copy number alteration of cfDNA. The COMOS was tested on 214 plasma samples of diffuse large B-cell lymphoma (DLBCL) and matched healthy controls.

RESULTS

For early diagnosis, COMOS improved the area under the curve (AUC) value to .993 compared with the individual omics model, with a sensitivity of 95% at 98% specificity. Detection sensitivity achieved 91% at 99% specificity in early-stage patients, while the AUC values of the individual omics model were 0.942, 0.968, 0.989, 0.935, 0.921, 0.781 and 0.917, respectively, with lower sensitivity and specificity. In the treatment response cohort, COMOS yielded a superior sensitivity of 88% at 86% specificity (AUC, 0.903). COMOS has achieved excellent performance in early diagnosis and treatment response prediction.

CONCLUSIONS

Our study provides an effectively improved approach with high accuracy for the diagnosis and prognosis of DLBCL, showing great potential for future clinical application.

KEY POINTS

A comprehensive multi-omics solution to specifically obtain an extensive fragmentomics landscape, presented by breakpoint characteristics of nucleosomes, CpG islands, DNase clusters and enhancers, besides typical methylation, copy number alteration of cfDNA. Integrated model of cfDNA multi-omics could be used for non-invasive early diagnosis of DLBCL. Integrated model of cfDNA multi-omics could effectively evaluate the efficacy of R-CHOP before DLBCL treatment.

摘要

背景

游离DNA（cfDNA）的多组学特征能够有效提高癌症无创早期诊断和预后评估的性能。然而，cfDNA的多模态表征在技术上仍具有挑战性。

方法

我们开发了一种综合多组学解决方案（COMOS），除了cfDNA的典型甲基化、拷贝数改变外，还能通过核小体、CpG岛、DNase簇和增强子的断点特征，专门获取广泛的片段组学图谱。该COMOS在214份弥漫性大B细胞淋巴瘤（DLBCL）血浆样本及匹配的健康对照样本上进行了测试。

结果

在早期诊断方面，与单个组学模型相比，COMOS将曲线下面积（AUC）值提高到了0.993，在特异性为98%时灵敏度为95%。在早期患者中，检测灵敏度在特异性为99%时达到91%，而单个组学模型的AUC值分别为0.942、0.968、0.989、0.935、0.921、0.781和0.917，灵敏度和特异性较低。在治疗反应队列中，COMOS在特异性为86%时灵敏度高达88%（AUC，0.903）。COMOS在早期诊断和治疗反应预测方面表现出色。