Identification of Crosstalk Genes Between Primary Sjögren’s Syndrome and Primary Biliary Cirrhosis by Transcriptome Analysis

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Abstract
Background Growing evidence points a connection between Primary Sjögren's Syndrome (pSS) and Primary Biliary Cholangitis (PBC). This study seeks to identify the crosstalk genes between them. Method Transcriptomic datasets for pSS (GSE66795) and PBC (GSE119600) were sourced from the Gene Expression Omnibus (GEO) database. Common genes between these two conditions were detected using Differential Expression Analysis and Weighted Gene Co-expression Network Analysis (WGCNA). Potential crosstalk genes were pinpointed through Least Absolute Shrinkage and Selection Operator (LASSO) regression. Validation of these genes were performed through single-sample gene set enrichment analysis (ssGSEA), multivariable logistic regression, and single-cell transcriptome analysis. Result Differential expression analysis showed 339 commonly upregulated DEGs in both pSS and PBC. WGCNA analysis revealed 11 modules associated with pSS and 7 modules associated with PBC. Subsequently, 56 core genes were found to overlap between the genes identified by differential expression analysis and WGCNA. LASSO regression identified CX3CR1, ELF1, CUL1, PARP3, DDX60, SP140L, and MUC1 as pivotal crosstalk genes for both pSS and PBC. Moreover, ssGSEA analysis and multivariable logistic regression underscored the potential of these 7 genes as crosstalk genes. Single-cell analyses revealed higher proportions of NK cells, CD4+ T cells, and CD8+ T cells in pSS patients, with prominent expression of CX3CR1, ELF1, CUL1, PARP3, DDX60, SP140L, and MUC1 in these cells. Conclusion Our study identified CX3CR1, ELF1, CUL1, PARP3, DDX60, SP140L and MUC1 as crosstalk genes between pSS and PBC, and highlighted the critical role of NK cells, CD4+ T cells and CD8+ T cells in disease mechanisms.
Funding Information
  • Chengdu University of Traditional Chinese Medicine Science and Technology Development Funding (23M219)
  • Chengdu University of Traditional Chinese Medicine Education Reform Program (JGJD202208)
  • Chengdu University of Traditional Chinese Medicine Hospital Education Reform Program (JGJX202209)
  • Sichuan provincial science and Technology Foundation (2021YFS0274)
  • Chengdu Municipal Science and Technology Program (2022-YF05-01896-SN)

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