Zhao Ye, Chen Xi, Huang Yuhan, Zhang Zhihan, Wang Kui, Zou Duowu, Ma Teng
Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
J Inflamm Res. 2024 Oct 28;17:7745-7760. doi: 10.2147/JIR.S479032. eCollection 2024.
This study aimed to investigate gene expression profiles, identify potential hub genes, and predict drugs for patients with erosive esophagitis (EE). Despite its clinical significance, molecular-level exploration of this condition has been limited.
RNA sequencing was performed on clinical biopsy samples from eight EE patients and eight healthy controls. Integrated bioinformatic tools were then utilized to analyze the data, including functional enrichment analysis, protein-protein interaction network analysis, weighted gene co-expression network analysis, immune infiltration analysis, and identification of small-molecule compounds. Additionally, the expressions of the identified hub genes were assessed in clinical samples.
A total of 2801 genes with differential expression were identified, including four potential hub genes: SOX9, SPP1, TIMP1, and TLR4. Moreover, the overexpression of these hub genes was verified in clinical samples. Analysis of Immune infiltration indicated an imbalance in the distribution of immune cell types in patients with EE. Correlation analysis between immune cells and hub genes unveiled noteworthy relationships. Specifically, SOX9 exhibited a negative correlation with CD8 T cells but a positive correlation with resting memory CD4 T cells. SPP1 displayed a positive correlation with naïve B cells, while TIMP1 exhibited a negative correlation with resting dendritic cells. Furthermore, the study identified ten small-molecule drugs with potential therapeutic effects for EE, including loreclezole and mercaptopurine.
This study provides valuable insights into the molecular understanding of EE, offering new perspectives on disease mechanisms. The findings may inspire further research leading to the development of novel treatment strategies for EE.
本研究旨在调查糜烂性食管炎(EE)患者的基因表达谱,识别潜在的枢纽基因,并预测相关药物。尽管其具有临床意义,但对该疾病的分子水平探索仍很有限。
对8例EE患者和8例健康对照的临床活检样本进行RNA测序。然后利用综合生物信息学工具分析数据,包括功能富集分析、蛋白质-蛋白质相互作用网络分析、加权基因共表达网络分析、免疫浸润分析以及小分子化合物的识别。此外,在临床样本中评估所识别枢纽基因的表达。
共鉴定出2801个差异表达基因,包括四个潜在的枢纽基因:SOX9、SPP1、TIMP1和TLR4。此外,这些枢纽基因的过表达在临床样本中得到验证。免疫浸润分析表明EE患者免疫细胞类型分布失衡。免疫细胞与枢纽基因的相关性分析揭示了值得注意的关系。具体而言,SOX9与CD8 T细胞呈负相关,但与静息记忆CD4 T细胞呈正相关。SPP1与幼稚B细胞呈正相关,而TIMP1与静息树突状细胞呈负相关。此外,该研究还确定了十种对EE具有潜在治疗作用的小分子药物,包括洛雷唑和巯嘌呤。
本研究为EE的分子理解提供了有价值的见解,为疾病机制提供了新的视角。这些发现可能会激发进一步的研究,从而开发出针对EE的新型治疗策略。