POS0353 DEEP PHENOTYPING OF PSORIASIS BASED ON LIPID METABOLISM RELATED GENES BY INTEGRATIVE SYSTEMS ANALYSIS
Authors: J. Shi, S. X. Zhang, J. Qiao, S. Song, R. Zhao, P. Zhao, G. Y. Liu, J. Luo, P. F. He, X. Li
Journal: Annals of the Rheumatic Diseases (2021)

Background: Psoriasis is an immune-mediated inflammatory, genetic disease with numerous concomitant metabolic disorders 1 . Patients with psoriasis experience substantial morbidity and increased rates of cardiometabolic diseases 2 . Among the metabolic disorders, lipid disturbances are recognized as a very important part in the pathogenesis of psoriasis and psoriasis-associated cardiometabolic diseases 3 4 . Objectives: To characterize the molecular features of psoriasis by the development of a classification system that was based on the gene expression profile of lipid metabolism related genes. Methods: We performed molecular subtyping and association analysis of psoriasis from Gene Expression Omnibus (GEO). The training sets includes GSE13355 cohort (N = 58), GSE14905 (N = 28) cohort and GSE30999 cohort (N = 81), while the GSE54456 (N = 92) was selected as the validation set. Energy metabolism-related genes were collected from MSigDB (version 7.0; http://software.broadinstitute.org/gsea/msigdb/ ). Based on these psoriasis lipid metabolism-related genes, we conducted consensus molecular subtyping with nonnegative matrix factorization (NMF). Finally, Gene set variation analysis (GSVA) was used to score individual subtypes against the metabolism-related gene sets, and each group got a GSVA index. Results: Total 104 lipid metabolism-related genes were clustered into three subgroups (Figure 1A). GSVA revealed the lipid metabolism with the correlation in subtypes. There was no statistical difference was identified between the subtype 1 and subtype 2(P &gt; 0.05, Figure 1B), so we merged the two types as a new Sub1, another subtype was named as the new Sub2 (Figure 1C). We finally identified 2 distinct subtypes of psoriasis in GEO cohort that were characterized by significantly different lipid metabolic gene score. Sub1 was featured by higher metabolic gene score compared with that of Sub2(P &lt; 0.001; Figure 1D). The lipid metabolic subtype classification was successfully validated in another independent patient cohorts (GSE54456). Conclusion: This study established a new classification based on the gene expression profiles of lipid metabolic genes, thereby furthering the understanding of the pathogenesis and psoriasis-associated diseases. References: [1]Boehncke WH, Schon MP. Psoriasis. Lancet 2015;386(9997):983-94. doi: 10.1016/S0140-6736(14)61909-7 [published Online First: 2015/05/31]. [2]Armstrong AW, Read C. Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review. JAMA 2020;323(19):1945-60. doi: 10.1001/jama.2020.4006 [published Online First: 2020/05/20]. [3]Goolam Mahyoodeen N, Crowther NJ, Pillay L, et al. Relationship of Visceral Fat and Adipokines with Cardiometabolic Diseases in Psoriasis. Acta Derm Venereol 2019;99(13):1218-23. doi: 10.2340/00015555-3327 [published Online First: 2019/10/04]. [4]Pietrzak A, Michalak-Stoma A, Chodorowska G, et al. Lipid disturbances in psoriasis: an update. Mediators Inflamm 2010;2010 doi: 10.1155/2010/535612 [published Online First: 2010/08/14]. Acknowledgements: This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078). Disclosure of Interests: None declared