Wang Ning, Yuan Ying, Jia Yanjun, Han Yue, Yu Xuemin, Fu Ying, Li Xiao
Department of Otolaryngology-Head and Neck Surgery, Qilu Hospital of Shandong University, Qingdao, China.
Department of Otolaryngology-Head and Neck Surgery, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, China.
Front Genet. 2024 Oct 8;15:1423778. doi: 10.3389/fgene.2024.1423778. eCollection 2024.
Chronic rhinosinusitis with nasal polyps (CRSwNP) belongs to a subtype of Chronic rhinosinusitis which is a heterogeneous inflammatory condition. It has been reported that mitophagy may provide a new therapeutic option for CRSwNP.
The GSE136825 (training dataset) and GSE179265 (validation dataset) were scoured from the Gene Expression Omnibus database. The candidate genes related to mitophagy were identified by differential expression analysis. Subsequently, the biomarkers were selected from the machine learning, Receiver Operating Characteristic curves, and expression level verification. A backpropagation (BP) neural network was generated to evaluate the diagnostic ability of biomarkers. In addition, the infiltration abundance of immune cells, potential drugs, and related ear-nose-throat (ENT) diseases were analyzed based on the biomarkers. Finally, qPCR analysis was performed to verify these biomarkers.
A total of 8 candidate genes were identified by overlapping 3,400 differentially expressed genes (DEGs) and 72 mitophagy-related genes Subsequently, TFE3 and TP53 were identified as biomarkers of CRSwNP, and the area under the curves (AUC) of the BP neural network was 0.74, which indicated that the biomarkers had excellent abilities. TFE3 and TP53 were co-enriched in the cancer pathway, cell cycle, endocytosis, etc. What's more, Macrophage and Immature dendritic cells had significant correlations with biomarkers. The drugs (Doxorubicin, Tetrachlorodibenzodioxin, etc.) and the ear-nose-throat diseases (hearing loss, sensorineural, tinnitus, etc.) related to biomarkers were predicted. Ultimately, qPCR results showed that the expression levels of TFE3 and TP53 in polyp tissue of CRSwNP were increased.
Overall, TFE3 and TP53 could be used as biomarkers or potential therapeutic targets to diagnose and treat CRSwNP.
伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）属于慢性鼻-鼻窦炎的一种亚型，慢性鼻-鼻窦炎是一种异质性炎症性疾病。据报道，线粒体自噬可能为CRSwNP提供一种新的治疗选择。
从基因表达综合数据库中筛选出GSE136825（训练数据集）和GSE179265（验证数据集）。通过差异表达分析确定与线粒体自噬相关的候选基因。随后，从机器学习、受试者工作特征曲线和表达水平验证中选择生物标志物。生成反向传播（BP）神经网络以评估生物标志物的诊断能力。此外，基于生物标志物分析免疫细胞的浸润丰度、潜在药物和相关耳鼻喉（ENT）疾病。最后，进行qPCR分析以验证这些生物标志物。
通过重叠3400个差异表达基因（DEG）和72个线粒体自噬相关基因，共鉴定出8个候选基因。随后，TFE3和TP53被鉴定为CRSwNP的生物标志物，BP神经网络的曲线下面积（AUC）为0.74，这表明这些生物标志物具有良好的能力。TFE3和TP53在癌症通路、细胞周期、内吞作用等方面共同富集。此外，巨噬细胞和未成熟树突状细胞与生物标志物有显著相关性。预测了与生物标志物相关的药物（阿霉素、四氯二苯并二恶英等）和耳鼻喉疾病（听力损失、感音神经性、耳鸣等）。最终，qPCR结果显示CRSwNP息肉组织中TFE3和TP53的表达水平升高。
总体而言，TFE3和TP53可作为诊断和治疗CRSwNP的生物标志物或潜在治疗靶点。
