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中国防痨杂志 ›› 2026, Vol. 48 ›› Issue (8): 1220-1225.doi: 10.19982/j.issn.1000-6621.20260161

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游离RNA液体活检在结核病分层诊断与动态监测中的研究进展

丁广招1, 刘荣梅2()   

  1. 1 北京市结核病胸部肿瘤研究所研究型病房, 北京 101149
    2 首都医科大学附属北京胸科医院研究型病房, 北京 101149
  • 收稿日期:2026-03-25 出版日期:2026-08-01 发布日期:2026-07-30
  • 通信作者: 刘荣梅,Email:Lrongmei@163.com
  • 基金资助:
    高层次公共卫生技术人才建设项目(学科骨干-03-49)

Cell-free RNA liquid biopsy for stratified diagnosis and dynamic monitoring of tuberculosis: research progress and translational challenges

Ding Guangzhao1, Liu Rongmei2()   

  1. 1 Research Ward, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China
    2 Research Ward, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China
  • Received:2026-03-25 Online:2026-08-01 Published:2026-07-30
  • Contact: Liu Rongmei, Email: Lrongmei@163.com
  • Supported by:
    High-level Public Health Technical Talents Construction Project(Discipline Backbone-03-49)

摘要:

结核病诊断与治疗监测仍面临多项关键挑战,包括少菌型及儿童病例病原学取样困难、活动性结核病与结核分枝杆菌潜伏感染鉴别不足,以及缺乏可重复、可动态评估疗效的分子指标。近年来,游离RNA(cell-free RNA,cfRNA)作为反映宿主免疫反应和转录调控状态的液体活检信号,在结核病分层诊断与动态监测中显示出应用潜力。但是,目前结核感染相关cfRNA的直接临床证据有限,主要体现在:样本量不足、病例-对照设计可能高估诊断性能、缺乏独立外部验证,以及真实世界临床增益评价缺失。本文围绕结核病临床管理中的核心任务,综述cfRNA在活动性结核病识别、结核分枝杆菌潜伏感染风险分层、治疗反应评估及特殊人群辅助诊断中的研究进展,归纳前分析处理、高丰度RNA去除、建库测序、靶向定量及模型构建与验证等关键技术环节对结果稳定性和临床转化性的影响,并进一步讨论其与现有病原学检测、免疫学检测及影像学评估的互补定位。

关键词: 结核, RNA, 诊断,鉴别, 生物学标记, 综述

Abstract:

The diagnosis and therapeutic monitoring of tuberculosis still face several critical challenges, including difficulties in etiological sampling for paucibacillary and pediatric cases, inadequate differentiation between active tuberculosis and latent tuberculosis infection, and the absence of reproducible molecular biomarkers for dynamic therapeutic response assessment. In recent years, cell-free RNA (cfRNA), a liquid biopsy signature reflecting host immune responses and transcriptional regulatory profiles, has demonstrated promising application potential in stratified diagnosis and longitudinal monitoring of tuberculosis. Nevertheless, direct clinical evidence supporting cfRNA for tuberculosis infection remains limited, mainly manifested as insufficient sample sizes, overestimated diagnostic performance arising from case-control study designs, lack of independent external validation, and the absence of evaluations on real-world clinical benefits. Centered on core clinical tasks in tuberculosis management, this review summarizes research advances of cfRNA in the identification of active tuberculosis, risk stratification of latent tuberculosis infection, therapeutic response evaluation, and auxiliary diagnosis among special populations. It also generalizes the impacts of key technical procedures—including pre-analytical processing, depletion of highly abundant RNA, library construction and sequencing, targeted quantification, as well as model development and validation—on result stability and clinical translatability. Furthermore, this paper discusses its complementary role alongside existing etiological tests, immunological assays and radiological assessments.

Key words: Tuberculosis, RNA, Diagnosis, differential, Biological markers, Review

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