Xu Zhaonan, Hao Qing, Yan Bingrui, Li Qiuying, Kan Xuan, Wu Qin, Yi Hongtian, Shen Xianji, Qu Lingmei, Wang Peng, Sun Yanan
Department of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Otolaryngology, Head and Neck Surgery, The Fifth Affiliated Hospital of Harbin Medical University, Daqing, China.
Sci Rep. 2025 Jun 3;15(1):19393. doi: 10.1038/s41598-025-02508-8.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent inflammatory disease where immunomodulation plays a pivotal role. However, immuno-transcriptomic characteristics and its clinical relevance remains largely known. We analyzed transcriptome data of 48 patients with CRSwNP and 34 healthy control subjects from different cohorts and investigated the immuno-transcriptomic characteristics. Differential immune-related genes (DIRGs) were identified and subjected to enrichment analysis. Protein-protein interaction (PPI) networks were constructed to identify hub genes. The least absolute shrinkage and selection operator (LASSO) regression model and multivariate support vector machine recursive feature elimination (mSVM-RFE) were used to identify potential biomarkers, which were validated using the real time quantitative polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). Infiltration abundance of immune cells in the microenvironment were estimated using CIBERSORT algorithm. Our study identified a total of 660 differentially expressed genes (DEGs) and 81 differentially immune-related genes (DIRGs) in CRSwNP compared to controls. Functional enrichment analysis revealed that the DIRGs were primarily associated with cell chemotaxis and leukocyte migration, and cytokine-cytokine receptor interaction. Through machine learning, we further identified five candidate genes, CXCR1, CCL13, CCR3, PPBP, and MMP9. These five potential CRSwNP biomarkers were experimentally verified in our in-house cohort. Analysis of immune cell infiltration landscape revealed significant variations in the abundance of macrophages and mast cells between CRSwNP and healthy control. Our findings illuminate the significance of immune characteristics in CRSwNP pathogenesis. Future studies focusing on these candidate genes can help elucidate the underlying mechanisms and identify potential therapeutic targets for CRSwNP.
伴有鼻息肉的慢性鼻-鼻窦炎（CRSwNP）是一种普遍的炎症性疾病，免疫调节在其中起着关键作用。然而，免疫转录组特征及其临床相关性在很大程度上仍不为人知。我们分析了来自不同队列的48例CRSwNP患者和34例健康对照受试者的转录组数据，并研究了免疫转录组特征。鉴定出差异免疫相关基因（DIRGs）并进行富集分析。构建蛋白质-蛋白质相互作用（PPI）网络以识别枢纽基因。使用最小绝对收缩和选择算子（LASSO）回归模型和多变量支持向量机递归特征消除（mSVM-RFE）来识别潜在的生物标志物，并通过实时定量聚合酶链反应（RT-PCR）和免疫组织化学（IHC）进行验证。使用CIBERSORT算法估计微环境中免疫细胞的浸润丰度。我们的研究发现，与对照组相比，CRSwNP中共有660个差异表达基因（DEGs）和81个差异免疫相关基因（DIRGs）。功能富集分析表明，DIRGs主要与细胞趋化性和白细胞迁移以及细胞因子-细胞因子受体相互作用有关。通过机器学习，我们进一步鉴定出五个候选基因，即CXCR1、CCL13、CCR3、PPBP和MMP9。这五个潜在的CRSwNP生物标志物在我们的内部队列中得到了实验验证。免疫细胞浸润格局分析显示，CRSwNP与健康对照之间巨噬细胞和肥大细胞的丰度存在显著差异。我们的研究结果阐明了免疫特征在CRSwNP发病机制中的重要性。未来针对这些候选基因的研究有助于阐明潜在机制，并确定CRSwNP的潜在治疗靶点。
