Jezernik Gregor, Gorenjak Mario, Potočnik Uroš
Faculty of Medicine, University of Maribor, Taborska ulica 8, 2000 Maribor, Slovenia.
Faculty of Chemistry and Chemical Engineering, University of Maribor, Smetanova ulica 17, 2000 Maribor, Slovenia.
Biomedicines. 2022 Jul 27;10(8):1808. doi: 10.3390/biomedicines10081808.
Anti-TNF therapy has significantly improved disease control in rheumatoid arthritis, but a fraction of rheumatoid arthritis patients do not respond to anti-TNF therapy or lose response over time. Moreover, the mechanisms underlying non-response to anti-TNF therapy remain largely unknown. To date, many single biomarkers of response to anti-TNF therapy have been published but they have not yet been analyzed as a system of interacting nodes. The aim of our study is to systematically elucidate the biological processes underlying non-response to anti-TNF therapy in rheumatoid arthritis using the gene ontologies of previously published predictive biomarkers. Gene networks were constructed based on published biomarkers and then enriched gene ontology terms were elucidated in subgroups using gene ontology software tools. Our results highlight the novel role of proteasome-mediated protein catabolic processes ( = 2.91 × 10) and plasma lipoproteins ( = 4.55 × 10) in anti-TNF therapy response. The results of our gene ontology analysis help elucidate the biological processes underlying non-response to anti-TNF therapy in rheumatoid arthritis and encourage further study of the highlighted processes.
抗TNF治疗显著改善了类风湿关节炎的疾病控制，但一部分类风湿关节炎患者对抗TNF治疗无反应或随时间推移失去反应。此外，抗TNF治疗无反应的潜在机制在很大程度上仍不清楚。迄今为止，许多抗TNF治疗反应的单一生物标志物已被发表，但它们尚未作为一个相互作用节点的系统进行分析。我们研究的目的是利用先前发表的预测生物标志物的基因本体，系统地阐明类风湿关节炎中抗TNF治疗无反应的潜在生物学过程。基于已发表的生物标志物构建基因网络，然后使用基因本体软件工具在亚组中阐明富集的基因本体术语。我们的结果突出了蛋白酶体介导的蛋白质分解代谢过程（= 2.91 × 10）和血浆脂蛋白（= 4.55 × 10）在抗TNF治疗反应中的新作用。我们的基因本体分析结果有助于阐明类风湿关节炎中抗TNF治疗无反应的潜在生物学过程，并鼓励对突出过程进行进一步研究。
