South China University of Technology School of Medicine, Guangzhou, 510006, China.
Department of Clinical Laboratory, Zhejiang Hospital, Hangzhou, 310013, China.
Biochem Biophys Res Commun. 2018 Sep 18;503(4):2263-2270. doi: 10.1016/j.bbrc.2018.06.147. Epub 2018 Jun 30.
This research aimed to discover potential biomarkers for evaluating the therapeutic efficacy of intensive therapy in pulmonary tuberculosis (TB). Protein profiles in 2-months intensively treated TB patients, untreated TB patients, and healthy controls were investigated with iTRAQ-2DLC-MS/MS technique. 71 differential proteins were identified in 2-months intensively treated TB patients. Significant differences in complement component C7 (CO7), apolipoprotein A-IV (APOA4), apolipoprotein C-II (APOC2), and angiotensinogen (ANGT) were found by ELISA validation. CO7 and ANGT were also found significantly different in sputum negative patients, compared with sputum positive patients after intensive treatment. Clinical analysis showed that after 2-months intensive treatment several indicators were significantly changed, and the one-year cure rate of sputum negative patients were significantly higher than sputum positive patients. Diagnostic models consisting of APOC2, CO7 and APOA4 were established to distinguish intensively treated TB patients from untreated TB patients and healthy controls with the AUC value of 0.910 and 0.935. Meanwhile, ANGT and CO7 were combined to identify sputum negative and sputum positive TB patients after intensive treatment with 89.36% sensitivity, 71.43% specificity, and the AUC value of 0.853. The results showed that APOC2, CO7, APOA4, and ANGT may be potential biomarkers for evaluating the efficacy of intensive anti-TB therapy.
本研究旨在发现用于评估肺结核(TB)强化治疗疗效的潜在生物标志物。采用 iTRAQ-2DLC-MS/MS 技术研究了 2 个月强化治疗 TB 患者、未治疗 TB 患者和健康对照者的蛋白质谱。在 2 个月强化治疗 TB 患者中鉴定出 71 个差异蛋白。通过 ELISA 验证发现补体成分 C7(CO7)、载脂蛋白 A-IV(APOA4)、载脂蛋白 C-II(APOC2)和血管紧张素原(ANGT)存在显著差异。CO7 和 ANGT 在强化治疗后痰阴性患者中也与痰阳性患者存在显著差异。临床分析表明,经过 2 个月的强化治疗,多项指标发生显著变化,痰阴性患者的 1 年治愈率明显高于痰阳性患者。由 APOC2、CO7 和 APOA4 组成的诊断模型能够区分强化治疗 TB 患者与未治疗 TB 患者和健康对照者,AUC 值分别为 0.910 和 0.935。同时,ANGT 和 CO7 联合可识别强化治疗后痰阴性和痰阳性 TB 患者,具有 89.36%的敏感性、71.43%的特异性和 0.853 的 AUC 值。结果表明,APOC2、CO7、APOA4 和 ANGT 可能是评估强化抗 TB 治疗疗效的潜在生物标志物。