基于 4D-DIA 的血浆蛋白质组分析评估骨关节炎早期治疗中对 Imrecoxib 的临床反应

IF 2.9 3区医学 Q2 RHEUMATOLOGY

Rheumatology and Therapy Pub Date : 2024-04-01 Epub Date: 2024-01-18 DOI:10.1007/s40744-023-00636-z

Han Xie, Yuan Zhang, Zunyi Zhu, Jingxuan Wei, Gulinigeer Ainiwaer, Weihong Ge

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引用次数: 0

摘要

导言：非甾体抗炎药（NSAIDs）是治疗骨关节炎（OA）的主要药物，但长期使用会产生不良反应，且疗效参差不齐。在非甾体抗炎药中，选择性环氧化酶-2（COX-2）抑制剂依来昔布可减少副作用，但对半数患者仍然无效。本研究旨在确定生物标志物，用于早期评估伊来昔布对 OA 的疗效，以优化个性化治疗：方法：2021年9月至2022年1月，南京鼓楼医院对OA患者进行了伊来昔布治疗。这些患者的血浆样本通过四维数据独立采集（4D-DIA）方法进行了蛋白质组学分析，随后进行了生物信息学分析。使用酶联免疫吸附试验（ELISA）对潜在的差异表达蛋白（DEPs）进行了验证：结果：共纳入 66 名膝关节 OA 患者，分为有反应者（35 人）和无反应者（31 人）。对每组中的 15 名患者进行了蛋白质组分析，并对每名患者进行了 ELISA 验证。我们发现两组患者在接受伊来昔布治疗后出现了 140 个 DEPs，其中 29 个蛋白上调，111 个蛋白下调（P ± 1.2）。经ELISA验证，确定了Galectin-1 (LGALS1)、galectin-3 (LGALS3)和分化簇44 (CD44)是评估OA患者对伊来昔布临床反应的潜在标志物：结论：本研究利用 4D-DIA 技术成功鉴定了用于评估 OA 患者对伊来昔布临床反应的生物标志物。这些生物标志物可能会在未来的个性化 OA 治疗策略中发挥重要作用，有待进一步证实。

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Plasma Proteomic Analysis Based on 4D-DIA Evaluates the Clinical Response to Imrecoxib in the Early Treatment of Osteoarthritis.

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the primary treatment for osteoarthritis (OA), but prolonged use has adverse effects and varying efficacy. Among NSAIDs, imrecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, reduces side effects yet remains ineffective for half of the patient population. This study aims to identify biomarkers for early evaluation of imrecoxib efficacy in OA for personalized therapy optimization.

Methods: From September 2021 to January 2022, imrecoxib was administered to patients with OA at Nanjing Drum Tower Hospital. Plasma samples from these patients underwent proteomic analysis through the four-dimensional data-independent acquisition (4D-DIA) method, followed by bioinformatics analysis. Potential differentially expressed proteins (DEPs) were validated using enzyme-linked immunosorbent assays (ELISA).

Results: Sixty-six patients with knee OA were included and divided into responders (n = 35) and non-responders (n = 31). Proteomic analysis was conducted on 15 patients from each group, with ELISA validation for every patient. We found 140 DEPs between the two groups after imrecoxib treatment, characterized by 29 proteins showing upregulation and 111 displaying downregulation (P < 0.05, fold change > ± 1.2). Galectin-1 (LGALS1), galectin-3 (LGALS3), and cluster of differentiation 44 (CD44) were identified as potential markers for evaluating clinical response to imrecoxib in OA following ELISA validation.

Conclusion: This study successfully identified biomarkers for evaluating imrecoxib's clinical response in patients with OA using 4D-DIA technology. These biomarkers may play a vital role in future personalized OA treatment strategies, pending further confirmation.

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来源期刊

Rheumatology and Therapy RHEUMATOLOGY-

CiteScore

6.00

自引率

5.30%

发文量

审稿时长

6 weeks

期刊介绍： Aims and Scope Rheumatology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of rheumatologic therapies. Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed. Areas of focus include, but are not limited to, rheumatoid arthritis, gout, gouty arthritis, psoriatic arthritis, osteoarthritis, juvenile idiopathic/rheumatoid arthritis, systemic lupus erythematosus, axial spondyloarthritis, Pompe’s disease, inflammatory joint conditions, musculoskeletal conditions, systemic sclerosis, and fibromyalgia. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial protocols, communications and letters. 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