Table_4_Genetic analysis of potential biomarkers and therapeutic targets in ferroptosis from psoriasis.xls

IntroductionFerroptosis is associated with multiple pathophysiological processes. Inhibition of ferroptosis has received much concern for some diseases. Nonetheless, there is no study comprehensively illustrating functions of ferroptosis-related genes (FRGs) in psoriasis.MethodsIn this study, FRGs together with psoriasis-associated data were obtained in Ferroptosis Database (FerrDb) and gene expression omnibus (GEO) database separately. This work identified altogether 199 psoriasis-associated DE-FRGs, and they were tightly associated with immunity and autophagy modulation. Thereafter, the present study utilized SVM-RFE and LASSO algorithms to identify NR5A2, CISD1, GCLC, PRKAA2, TRIB2, ABCC5, ACSF2, TIMM9, DCAF7, PEBP1, and MDM2 from those 199 DE-FRGs to be marker genes. As revealed by later functional annotation, the marker genes possibly had important effects on psoriasis through being involved in diverse psoriasis pathogenesis-related pathways such as cell cycle, toll-like receptor (TLR), chemokine, and nod-like receptor (NLR) pathways. Moreover, altogether 37 drugs that targeted 11 marker genes were acquired. Besides, based on CIBERSORT analysis, alterations of immune microenvironment in psoriasis cases were possibly associated with PRKAA2, PEBP1, CISD1, and ACSF2.DiscussionTaken together, this work established the diagnostic potency and shed more lights on psoriasis-related mechanism. More investigations are warranted to validate its value in diagnosing psoriasis before it is applied in clinic.

铁死亡与多种病理生理过程密切相关。针对铁死亡的抑制已引起诸多疾病的广泛关注。然而，目前尚无研究能够全面阐述铁死亡相关基因（FRGs）在银屑病中的功能。方法在本研究中，我们从铁死亡数据库（FerrDb）和基因表达综合数据库（GEO）中分别获取了FRGs以及与银屑病相关的数据。本研究共鉴定出199个与银屑病相关的差异表达FRGs，它们与免疫调节和自噬调控密切相关。随后，本研究利用支持向量机递归特征消除（SVM-RFE）和LASSO算法从这199个差异表达FRGs中筛选出NR5A2、CISD1、GCLC、PRKAA2、TRIB2、ABCC5、ACSF2、TIMM9、DCAF7、PEBP1和MDM2作为标记基因。通过后续的功能注释，这些标记基因可能通过参与多种与银屑病发病机制相关的途径，如细胞周期、Toll样受体（TLR）、趋化因子和nod样受体（NLR）途径，对银屑病产生重要影响。此外，还收集了针对11个标记基因的37种药物。此外，基于CIBERSORT分析，银屑病患者免疫微环境的改变可能与PRKAA2、PEBP1、CISD1和ACSF2相关。讨论综上所述，本研究确立了诊断的潜力并为进一步阐明银屑病相关机制提供了新的洞见。在临床应用之前，有必要进行更多研究以验证其在诊断银屑病中的价值。