Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, China.
Yuebei People's Hospital, Shaoguan, China.
J Cell Mol Med. 2020 Nov;24(21):12537-12549. doi: 10.1111/jcmm.15796. Epub 2020 Sep 23.
Multidrug-resistant tuberculosis (MDR-TB), defined as tuberculosis (TB) resistant to at least isoniazid and rifampicin, is a major concern of TB control worldwide. However, the diagnosis of MDR-TB remains a huge challenge to its prevention and control. To identify new diagnostic methods for MDR-TB, a mass spectrometry strategy of data-independent acquisition and parallel reaction monitoring was used to detect and validate differential serum proteins. The bioinformatic analysis showed that the functions of differential serum proteins between the MDR-TB group and the drug-sensitive tuberculosis group were significantly correlated to the complement coagulation cascade, surface adhesion and extracellular matrix receptor interaction, suggesting a disorder of coagulation in TB. Here, we identified three potential candidate biomarkers such as sCD14, PGLYRP2 and FGA, and established a diagnostic model using these three candidate biomarkers with a sensitivity of 81.2%, a specificity of 90% and the area under the curve value of 0.934 in receiver operation characteristics curve to diagnose MDR-TB. Our study has paved the way for a novel method to diagnose MDR-TB and may contribute to elucidate the mechanisms underlying MDR-TB.
耐多药结核病（MDR-TB）是指至少对异烟肼和利福平耐药的结核病，是全球结核病控制的主要关注点。然而，MDR-TB 的诊断仍然是其预防和控制的巨大挑战。为了寻找 MDR-TB 的新诊断方法，本研究采用数据非依赖性采集和并行反应监测的质谱策略，以检测和验证差异血清蛋白。生物信息学分析表明，MDR-TB 组和药敏结核病组之间差异血清蛋白的功能与补体凝血级联、表面黏附和细胞外基质受体相互作用显著相关，表明结核病存在凝血紊乱。在此，我们鉴定了三个潜在的候选生物标志物，如 sCD14、PGLYRP2 和 FGA，并使用这三个候选生物标志物建立了一个诊断模型，该模型的诊断 MDR-TB 的灵敏度为 81.2%，特异性为 90%，ROC 曲线下面积值为 0.934。本研究为诊断 MDR-TB 开辟了新方法，可能有助于阐明 MDR-TB 的发病机制。
