Del Real Alvaro, Ciordia Sergio, Sañudo Carolina, Garcia-Ibarbia Carmen, Roa-Bautista Adriel, Ocejo-Viñals Javier G, Corrales Fernando, Riancho Jose A
Departamento de Medicina y Psiquiatría, Universidad de Cantabria, IDIVAL, 39008 Santander, Spain.
Laboratorio de Proteómica Funcional, Centro Nacional de Biotecnología-CSIC, Proteored-ISCIII, 28049 Madrid, Spain.
Metabolites. 2022 Apr 28;12(5):399. doi: 10.3390/metabo12050399.
The aim of the study was to explore new markers in serum proteome associated with the response to antiosteoporosis drugs, namely teriparatide and denosumab. We obtained serum samples from 14 patients with osteoporosis, both at baseline and after 6 months of treatment with teriparatide (n = 10) or denosumab (n = 4). Samples were analyzed by nanoliquid chromatography coupled to high-resolution mass spectrometry on a QTOF 5600 (SCIEX) apparatus. The spectrometry data were analyzed with Mascot against the UniProtKB base and then several quality-control filters were applied for the identification of peptides (false discovery rate, FDR q < 0.02) and their quantification (FDR q < 0.05). In the group treated with teriparatide, 28 proteins were identified with significant differences before and after treatment. A pathway analysis by using the Reactome database revealed significant enrichment in the Insulin Like Growth Factor 1 (IGF-I) (FDR q 4 × 10−2) and innate immune system (FDR q 2 × 10−3) pathways. Among patients treated with denosumab, we observed significant differences in the levels of 10 proteins, which were also enriched in the pathways related to the innate immune system (FDR q 3 × 10−2). These results suggest that the innate immune system may be involved in the response to antiosteoporosis drugs.
本研究的目的是探索血清蛋白质组中与抗骨质疏松药物（即特立帕肽和地诺单抗）反应相关的新标志物。我们从14名骨质疏松患者中获取了血清样本，分别在基线时以及使用特立帕肽（n = 10）或地诺单抗（n = 4）治疗6个月后采集。样本在QTOF 5600（SCIEX）仪器上通过纳升液相色谱与高分辨率质谱联用进行分析。质谱数据使用Mascot软件针对UniProtKB数据库进行分析，然后应用多个质量控制过滤器来鉴定肽段（错误发现率，FDR q < 0.02）及其定量（FDR q < 0.05）。在接受特立帕肽治疗的组中，鉴定出28种蛋白质在治疗前后存在显著差异。使用Reactome数据库进行的通路分析显示，胰岛素样生长因子1（IGF-I）通路（FDR q 4 × 10−2）和先天免疫系统通路（FDR q 2 × 10−3）有显著富集。在接受地诺单抗治疗的患者中，我们观察到10种蛋白质的水平存在显著差异，这些蛋白质也在与先天免疫系统相关的通路中富集（FDR q 3 × 10−2）。这些结果表明，先天免疫系统可能参与了对抗骨质疏松药物的反应。
