Nie Liu-Yan, Zhao Kun, Xu Cheng, Zhang Wen-Juan, Huang Xin, Han Yong-Mei
Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research, Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China.
Cell Biochem Funct. 2025 Jan;43(1):e70033. doi: 10.1002/cbf.70033.
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is an increasingly recognized extra-articular manifestations (EAMs) in the RA, with highly morbidity and mortality. The identification of key molecules involved in RA-ILD has a high requirement in clinic, and the role of their transcriptional regulation in the etiology of RA-ILD is great significant for investigation. In this study, we collected the whole peripheral blood samples of RA-ILD and RA only patients to bulk RNA-sequence. Differential gene expression analysis was employed to identify key genes, common pathways, and potential drug targets for RA-ILD. Furthermore, RT-qPCR was conducted to verify potential biomarkers in RA-ILD. Four hundred seventy-eight differentially expressed genes (DEGs) were identified that related to chromatin-modifying enzymes. A robust correlation with immune and inflammation biological processes and pathways was indicated through enrichment analyses of these shared DEGs, like B cell receptor signaling pathway, complement activation, NF-kappa B signaling pathway. Protein-protein interaction network analysis further emphasized the significance of 12 hub genes, including CHD4, MUS81, CXCL8, NSUN6, RAD9A, CCL4, B3GAT1, KAT2A, TBX21, HDAC2, ERBB2, and ITGAL. Notably, NSUN6 expression was statistically significant in RA-ILD by the machine learning LASSO regression analysis and RT-qPCR. Our study provides novel insights into the molecular mechanisms of RA-ILD, identifies potential biomarkers, and lays the groundwork for future therapeutic strategies.
类风湿关节炎相关间质性肺疾病（RA-ILD）是类风湿关节炎（RA）中一种日益受到认可的关节外表现（EAMs），具有较高的发病率和死亡率。鉴定参与RA-ILD的关键分子在临床上有很高的要求，并且它们的转录调控在RA-ILD病因学中的作用对于研究具有重要意义。在本研究中，我们收集了RA-ILD患者和仅患RA患者的全外周血样本进行批量RNA测序。采用差异基因表达分析来鉴定RA-ILD的关键基因、共同通路和潜在药物靶点。此外，进行RT-qPCR以验证RA-ILD中的潜在生物标志物。鉴定出478个与染色质修饰酶相关的差异表达基因（DEGs）。通过对这些共享DEGs的富集分析表明，它们与免疫和炎症生物学过程及通路有密切相关性，如B细胞受体信号通路、补体激活、核因子κB信号通路。蛋白质-蛋白质相互作用网络分析进一步强调了12个枢纽基因的重要性，包括CHD4、MUS81、CXCL8、NSUN6、RAD9A、CCL4、B3GAT1、KAT2A、TBX21、HDAC2、ERBB2和ITGAL。值得注意的是，通过机器学习LASSO回归分析和RT-qPCR，NSUN6在RA-ILD中的表达具有统计学意义。我们的研究为RA-ILD的分子机制提供了新的见解，鉴定了潜在的生物标志物，并为未来的治疗策略奠定了基础。
