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Background <p>Interstitial lung disease (ILD) is a severe pulmonary complication of primary Sjögren's Syndrome (pSS), associated with significant morbidity and mortality. Identifying molecular markers and hub genes in pSS-associated ILD (pSS-ILD) may provide novel therapeutic targets.</p> Methods <p>Peripheral blood mononuclear cells (PBMCs) were collected from pSS patients (<i>n</i> = 9), pSS-ILD patients (<i>n</i> = 6), and healthy controls (<i>n</i> = 15) for transcriptome sequencing. Differentially expressed genes (DEGs) were identified between pSS and controls (DEGs-SS) and between pSS-ILD and pSS groups (DEGs-SS-ILD). Overlapping DEGs were analyzed to identify hub genes using Cytohubba in Cytoscape. Functional enrichment, gene set enrichment analysis (GSEA), Spearman’s correlation analysis, and immune infiltration analyses were performed. Potential drugs targeting hub genes were predicted, and molecular docking was conducted. Hub gene expression was validated using reverse transcription quantitative PCR (RT-qPCR).</p> Results <p>A total of 932 DEGs-SS and 186 DEGs-SS-ILD were identified, with 78 overlapping genes. Five hub genes (IFIT2, IFIT3, LY6E, IFI27, and ISG15) were identified. IFIT2-IFIT3 and ISG15-LY6E showed strong expression correlations (correlation coefficient = 0.943,&#xa0;<i>p</i> &lt; 0.05) and functional similarities. Immune infiltration analysis revealed a significant decrease in resting natural killer (NK) cells in pSS patients compared to controls, which was further reduced in pSS-ILD patients. Bisphenol A was identified as a potential therapeutic compound targeting IFIT3, IFIT2, LY6E, and IFI27, with high binding affinity (binding energy = -6.26&#xa0;kJ/mol). RT-qPCR validation confirmed the differential expression of hub genes, consistent with bioinformatics findings.</p> Conclusion <p>The hub genes IFIT2, IFIT3, LY6E, IFI27, and ISG15 represent potential biomarkers and therapeutic targets for pSS-ILD. These findings provide novel insights into the molecular mechanisms and potential treatments for pSS-ILD.</p>

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Identification of five novel hub genes associated with interstitial lung disease in primary Sjögren's syndrome via transcriptome sequencing

  • 期刊论文

  • 发表日期：

    2025年11月10日

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  • Zhou Junfei,
  • Zhao zhen,
  • Qiang Fu,
  • Gao meihua,
  • Lei zhidan,
  • Liu yajing,
  • TianShu Chu,
  • Shi lipu

摘要

Background

Interstitial lung disease (ILD) is a severe pulmonary complication of primary Sjögren's Syndrome (pSS), associated with significant morbidity and mortality. Identifying molecular markers and hub genes in pSS-associated ILD (pSS-ILD) may provide novel therapeutic targets.

Methods

Peripheral blood mononuclear cells (PBMCs) were collected from pSS patients (n = 9), pSS-ILD patients (n = 6), and healthy controls (n = 15) for transcriptome sequencing. Differentially expressed genes (DEGs) were identified between pSS and controls (DEGs-SS) and between pSS-ILD and pSS groups (DEGs-SS-ILD). Overlapping DEGs were analyzed to identify hub genes using Cytohubba in Cytoscape. Functional enrichment, gene set enrichment analysis (GSEA), Spearman’s correlation analysis, and immune infiltration analyses were performed. Potential drugs targeting hub genes were predicted, and molecular docking was conducted. Hub gene expression was validated using reverse transcription quantitative PCR (RT-qPCR).

Results

A total of 932 DEGs-SS and 186 DEGs-SS-ILD were identified, with 78 overlapping genes. Five hub genes (IFIT2, IFIT3, LY6E, IFI27, and ISG15) were identified. IFIT2-IFIT3 and ISG15-LY6E showed strong expression correlations (correlation coefficient = 0.943, p < 0.05) and functional similarities. Immune infiltration analysis revealed a significant decrease in resting natural killer (NK) cells in pSS patients compared to controls, which was further reduced in pSS-ILD patients. Bisphenol A was identified as a potential therapeutic compound targeting IFIT3, IFIT2, LY6E, and IFI27, with high binding affinity (binding energy = -6.26 kJ/mol). RT-qPCR validation confirmed the differential expression of hub genes, consistent with bioinformatics findings.

Conclusion

The hub genes IFIT2, IFIT3, LY6E, IFI27, and ISG15 represent potential biomarkers and therapeutic targets for pSS-ILD. These findings provide novel insights into the molecular mechanisms and potential treatments for pSS-ILD.