Exploration of the molecular mechanisms, shared gene signatures, and MicroRNAs between systemic lupus erythematosus and diffuse large B cell lymphoma by bioinformatics analysis

• Published in: Lupus Vol. 31; no. 11; pp. 1317 - 1327
• Main Authors: Peng, Zhishen, Liang, Xiaofeng, Lin, Xiaobing, Lin, Weiyi, Lin, Zien, Wei, Shanshan
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.10.2022; Sage Publications Ltd
• Subjects: Autoimmune diseases; B-cell lymphoma; Bioinformatics; Computer programs; DNA microarrays; Gene expression; Lupus; Lymphoma; MicroRNAs; miRNA; Molecular modelling; NF-κB protein; Pathophysiology; Systemic lupus erythematosus; Therapeutic targets; diagnostic markers; miRNA; systemic lupus erythematosus; diffuse large B cell lymphoma; NF-κB pathway
• ISSN: 0961-2033; 1477-0962
• DOI: 10.1177/09612033221114578

Background Systemic lupus erythematosus (SLE) is a complex heterogeneous systemic autoimmune disease. Previous studies have shown that SLE may be related to diffuse large B cell lymphoma (DLBCL), but the mechanism of their relationship is still unclear. The present study aimed to explore the common genetic molecular mechanisms, core shared genes, and miRNAs between SLE and DLBCL as well as to investigate the diagnostic markers of DLBCL. Methods The SLE and DLBCL microarray data were downloaded from the comprehensive Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was used to identify co-expression modules. Four core shared genes were screened out by various algorithms and validated in other cohorts. Finally, we constructed a common core gene-miRNA network using the human microRNA disease database (HMDD) and TarBase. Results Using WGCNA, four modules were identified as important modules for SLE and DLBCL. Enrichment analysis of the shared genes showed that the highly activated NF-κB pathway was a common feature of the pathophysiology. Four core shared genes, namely, PSMB10, PSMB4, TAF10, and NFΚBIA, were screened out. These core shared genes were significantly upregulated in both diseases, and they may be potential diagnostic markers of DLBCL. The core gene-miRNA network showed that miR-155–5p, regulating the shared NF-κB pathway, may play an important role in the susceptibility of SLE patients to DLBCL. Conclusion The present study revealed that NF-κB pathway in SLE may be a crucial susceptible factor for DLBCL. In addition, we identified PSMB10, PSMB4, TAF10, NFΚBIA and miR-155 involved in the common pathogenesis as potential biomarkers and therapeutic targets for DLBCL.