研究发现Cadherin11在风湿性关节炎患者关节滑膜细胞中特异性表达，并参与疾病发病机制。通过对公开转录组数据的分析，揭示了纤维母细胞、巨噬细胞、淋巴细胞和破骨细胞等基因签名在RA患者中的富集，并发现Cadherin11与这些病理过程相关。此外，Cadherin11表达与脂肪细胞相关基因签名呈负相关，为未来RA治疗靶点和生物标志物的开发提供了新线索。
摘要：
Introduction Cadherin 11 is selectively expressed by synovial fibroblasts and plays a role in the pathogenesis of rheumatoid arthritis (RA).1 Consequently, blocking cadherin 11 function in inflamed tissues may represent a potentially effective and novel therapy for RA. Objectives Here we interrogated publicly available transcriptomics datasets from RA patients synovial tissue and healthy controls using pre-defined primary cell gene signatures to better understand the heterogeneity of the underlying pathology. In addition, we analysed the association of these gene signatures with the expression of cadherin 11 gene to narrow down the underlying mechanistic network on which targeted treatments and biomarkers can be developed. Methods We used two publicly available transcriptomics studies from NCBI Gene Expression Omnibus2 performed on synovial tissue of RA patients and healthy controls: GSE7307 (RA=5, healthy=7) and GSE77298 (RA=16, healthy=7). The pre-defined gene signatures were derived from ENCODE primary cell expression data3 and signature enrichment was applied using the BioQC package.4Principal component analysis (PCA) was applied on the BioQC enrichment scores to (i) identify potential clusters of samples and to (ii) identify the gene signatures responsible for the clustering. In addition, associations between cadherin 11 gene expression and gene signatures were tested. Results In both studies, cadherin 11 was higher expressed in RA patients compared to healthy controls. PCA performed on gene enrichment scores showed RA patients clustered apart from the healthy controls. Moreover, fibroblast, macrophage, lymphocyte and osteoclast gene signatures were significantly enriched in the RA patients compared to healthy controls in both studies. Unexpectedly, an adipokine-related signature was significantly enriched in RA patients from one transcriptomics dataset (GSE77298), while only showing a trend in the second set (GSE7037). In addition, in both studies Cadherin 11 was associated positively with fibroblast and lymphocyte signatures and negatively with adipokines-related signature. Conclusions The identified cadherin 11 related gene signatures expand our knowledge on cadherin 11 biology in human RA and may serve as potential biomarkers for RA studies in the future. References . Lee, et al. Science 2007;315:1006–10. . https://www.ncbi.nlm.nih.gov/geo/ . ENCODE Project Consortium. Nature2012;489(7414):57–74. . Zhang, et al. BMC Genomics2017;18(1):277. Disclosure of interest K. Hatje Employee of: Roche, T. Kam-Thong Employee of: Roche, D. Hartl Employee of: Roche, G. Duchateau-Nguyen Employee of: Roche
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