Anis Mursalin M, Griswold Anthony J, Soliman Ahmed M S, Liu Xue Zhong, Rosow David E
Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, USA.
Department of Human Genetics, John P. Hussman Institute for Human Genomics, Miami, Florida, USA.
Laryngoscope. 2025 Aug 19. doi: 10.1002/lary.70057.
Determination of differential gene expression in idiopathic subglottic stenosis.
Subglottic and tracheal tissues were collected from 19 prospectively recruited patients with laryngotracheal stenosis undergoing surgery: 11 patients with idiopathic subglottic stenosis (iSGS) and 8 patients with post-intubation laryngotracheal stenosis (iLTS). Total RNA was extracted from specimens. Bulk RNA sequencing (RNAseq) was done. Differential gene expression analyses were carried out using DESeq2. Bioinformatic approaches were utilized to gain insight into pathways significant for iSGS.
There were 68 differentially expressed genes (DEGs) between iSGS females and iLTS females. Gene Set Enrichment Analysis (GSEA) revealed that epithelial-mesenchymal transition (EMT) was the most upregulated pathway in iSGS pathogenesis compared to iLTS. The most downregulated pathway in iSGS compared to iLTS was TNFα signaling via NF-κB. Candidate DEGs in iSGS were selected based on GSEA of Hallmark gene sets. Gene Ontology enrichment analysis of these 32 candidate DEGs revealed that significant biological pathways included cell-cell adhesion and neutrophil aggregation. KEGG database identified IL-17 signaling to be the most enriched pathway among the candidate genes.
This pilot study corroborated the significance of EMT as the most upregulated pathway in iSGS. Inflammatory pathways were more upregulated in the pathogenesis of iLTS compared to iSGS. Candidate DEGs encoding integral membrane proteins were downregulated in iSGS compared to iLT. IL-17 signaling played an important role in both iSGS and iLTS. The roles of innate immunity remain to be defined in iSGS.
确定特发性声门下狭窄中的差异基因表达。
从19例前瞻性招募的接受手术的喉气管狭窄患者中收集声门下和气管组织：11例特发性声门下狭窄（iSGS）患者和8例插管后喉气管狭窄（iLTS）患者。从标本中提取总RNA。进行批量RNA测序（RNAseq）。使用DESeq2进行差异基因表达分析。利用生物信息学方法深入了解对iSGS有重要意义的通路。
iSGS女性和iLTS女性之间有68个差异表达基因（DEG）。基因集富集分析（GSEA）显示，与iLTS相比，上皮-间质转化（EMT）是iSGS发病机制中上调最明显的通路。与iLTS相比，iSGS中下调最明显的通路是通过NF-κB的TNFα信号传导。基于标志性基因集的GSEA选择iSGS中的候选DEG。对这32个候选DEG进行基因本体富集分析，结果显示重要的生物学通路包括细胞-细胞粘附和中性粒细胞聚集。KEGG数据库确定IL-17信号传导是候选基因中富集最明显的通路。
这项初步研究证实了EMT作为iSGS中上调最明显的通路的重要性。与iSGS相比，炎症通路在iLTS发病机制中上调更明显。与iLT相比，编码整合膜蛋白的候选DEG在iSGS中下调。IL-17信号传导在iSGS和iLTS中均起重要作用。先天性免疫在iSGS中的作用仍有待确定。
