Haoguang Li, Jie Zhou, Lu Zhou, Xiuling Zhang, Jingjing Shang, Xueqin Feng, Le Yu, Jie Fan, Jie Ren, Rongwei Zhang, Xinwang Duan

Identification of the shared gene signatures and molecular pathways in systemic lupus erythematosus and diffuse large B‐cell lymphoma

  • Genetics (clinical)
  • Drug Discovery
  • Genetics
  • Molecular Biology
  • Molecular Medicine
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AbstractBackgroundDiffuse large B‐cell lymphoma (DLBCL) incidence is higher in systemic lupus erythematosus (SLE) patients than the general population, but the molecular mechanisms behind this link remain ambiguous. The aim of this study was to investigate shared gene signatures and molecular pathways between SLE and DLBCL.MethodsWe procured expression profiles of SLE and DLBCL from public databases and identified common differentially expressed genes (DEGs). Functional pathway enrichment and protein–protein interaction (PPI) analyses were performed on these shared genes. The molecular complex detection technology (MCODE) and eXtreme Gradient Boosting (XGBoost) machine learning algorithm were used to select core shared genes, followed by Gene Set Enrichment Analysis (GSEA) and immune infiltration analysis.ResultsWe identified 54 DEGs as shared genes, among which CD177, CEACAM1, GPR84 and IFIT3 were identified as core shared genes. These genes showed strong associations with inflammatory and immune response pathways. We found a significant positive correlation between GPR84 and IFIT3 expression levels and the immune microenvironment. Decreased expression levels of GPR84 and IFIT3 were linked to enhanced immune therapy sensitivity, potentially due to lower dysregulation scores during low expression. We also discovered that TP53 mutations might elevate CD177 and GPR84 expression and that reduced expression levels of GPR84 and IFIT3 were linked with better overall survival and progression‐free survival in DLBCL patients.ConclusionsOur study provides valuable insights into the shared molecular mechanisms underpinning the pathogenesis of SLE and DLBCL. These findings could potentially offer new biomarkers and therapeutic targets for SLE and DLBCL.

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