Deng Min, Su Yuwen, Wu Ruifang, Li Siying, Zhu Yanshan, Tang Guishao, Shi Xiaoli, Zhou Tian, Zhao Ming, Lu Qianjin
Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, China.
Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, China.
J Dermatol Sci. 2022 Oct;108(1):39-47. doi: 10.1016/j.jdermsci.2022.11.001. Epub 2022 Nov 10.
The clinical manifestations of psoriatic arthritis (PsA) are highly heterogeneous and no reliable diagnostic biomarkers exist.
We explored the role of DNA methylation CpG markers in the diagnosis of PsA.
DNA methylation array was used to screen for differentially methylated sites (DMSs) in the discovery phase (PsA, n = 25; healthy controls [HCs], n = 19; psoriasis vulgaris [PsV], n = 20). In the validation phase, pyrosequencing was used to identify the DMSs in an expanded cohort (PsA, n = 60; HCs, n = 91; PsV, n = 48; rheumatoid arthritis [RA], n = 60). Logistic regression prediction models were established based on the identified DMSs for the diagnosis of PsA.
A total of 17 DMSs differentiating PsA and HCs as well as 11 DMSs differentiating PsA and PsV were screened in the discovery phase. A total of six DMSs (chr14: cg07940072, chr14: 38061320, chr9: cg15734589, chr6: cg12800266, chr3: cg12992827, chr6: cg24500972) differentiating PsA and HCs and two DMSs (chr12: cg16459382, chr2: cg16348668) differentiating PsA and PsV were identified using pyrosequencing. Three logistic regression prediction models were established based on the identified DMSs, which distinguished PsA, RA, PsV, and HCs (P < 0.001). The models performed well in differentiating PsA from HCs, RA, and PsV (AUC: 0.858, 0.851, and 0.976, respectively).
The models based on methylated CpG sites are useful for distinguishing patients with PsA from HCs and those with RA or PsV and are a highly sensitive and specific diagnostic biomarker for PsA.
银屑病关节炎(PsA)的临床表现高度异质性,且不存在可靠的诊断生物标志物。
我们探讨了DNA甲基化CpG标记物在PsA诊断中的作用。
在发现阶段(PsA,n = 25;健康对照[HCs],n = 19;寻常型银屑病[PsV],n = 20),使用DNA甲基化芯片筛选差异甲基化位点(DMSs)。在验证阶段,采用焦磷酸测序法在一个扩大的队列中鉴定DMSs(PsA,n = 60;HCs,n = 91;PsV,n = 48;类风湿关节炎[RA],n = 60)。基于鉴定出的DMSs建立逻辑回归预测模型用于PsA的诊断。
在发现阶段筛选出17个区分PsA和HCs的DMSs以及11个区分PsA和PsV的DMSs。通过焦磷酸测序鉴定出6个区分PsA和HCs的DMSs(chr14: cg07940072、chr14: 38061320、chr9: cg15734589、chr6: cg12800266、chr3: cg12992827、chr6: cg24500972)和2个区分PsA和PsV的DMSs(chr12: cg16459382、chr2: cg16348668)。基于鉴定出的DMSs建立了3个逻辑回归预测模型,可以区分PsA、RA、PsV和HCs(P < 0.001)。这些模型在区分PsA与HCs、RA和PsV方面表现良好(AUC分别为0.858、0.851和0.976)。
基于甲基化CpG位点的模型有助于区分PsA患者与HCs以及RA或PsV患者,并是PsA的一种高度敏感和特异的诊断生物标志物。