Wang Huikang, Xu Xinjun, Lu Haoran, Zheng Yang, Shao Liting, Lu Zhaoyang, Zhang Yu, Song Xicheng
Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, QingdaoUniversity, Yantai, People's Republic of China.
Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, People's Republic of China.
J Inflamm Res. 2024 Oct 22;17:7573-7590. doi: 10.2147/JIR.S484914. eCollection 2024.
The pathogenesis of CRSwNP is complex and not yet fully explored, so we aimed to identify the pivotal hub genes and associated pathways of CRSwNP, to facilitate the detection of novel diagnostic or therapeutic targets.
Utilizing two CRSwNP sequencing datasets from GEO, differential expression gene analysis, WGCNA, and three machine learning methods (LASSO, RF and SVM-RFE) were applied to screen for hub genes. A diagnostic model was then formulated utilizing hub genes, and the AUC was generated to evaluate the performance of the prognostic model and candidate genes. Hub genes were validated through the validation set and qPCR performed on normal mice and CRSwNP mouse model. Lastly, the ssGSEA algorithm was employed to assess the differences in immune infiltration levels.
A total of 239 DEGs were identified, with 170 upregulated and 69 downregulated in CRSwNP. Enrichment analysis revealed that these DEGs were primarily enriched in pathways related to nucleocytoplasmic transport and HIF-1 signaling pathway. Data yielded by WGCNA analysis contained 183 DEGs. The application of three machine learning algorithms identified 11 hub genes. Following concurrent validation analysis with the validation set and qPCR performed after establishing the mouse model confirmed the overexpression of BTBD10, ERAP1, GIPC1, and PEX6 in CRSwNP. The examination of immune cell infiltration suggested that the infiltration rate of type 2 T helper cell and memory B cell experienced a decline in the CRSwNP group. Conversely, the infiltration rates of Immature dendritic cell and Effector memory CD8 T cell were positive correlation.
This study successfully identified and validated BTBD10, ERAP1, GIPC1, and PEX6 as potential novel diagnostic or therapeutic targets for CRSwNP, which offers a fresh perspective and a theoretical foundation for the diagnostic prediction and therapeutic approach to CRSwNP.
慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）的发病机制复杂且尚未完全阐明，因此我们旨在识别CRSwNP的关键枢纽基因和相关通路，以促进新型诊断或治疗靶点的发现。
利用来自基因表达综合数据库（GEO）的两个CRSwNP测序数据集，应用差异表达基因分析、加权基因共表达网络分析（WGCNA）以及三种机器学习方法（套索回归、随机森林和支持向量机递归特征消除法）筛选枢纽基因。然后利用枢纽基因构建诊断模型，并生成曲线下面积（AUC）以评估预后模型和候选基因的性能。通过验证集以及对正常小鼠和CRSwNP小鼠模型进行定量聚合酶链反应（qPCR）来验证枢纽基因。最后，采用单样本基因集富集分析（ssGSEA）算法评估免疫浸润水平的差异。
共鉴定出239个差异表达基因（DEG），其中170个在CRSwNP中上调，69个下调。富集分析显示，这些DEG主要富集在与核质运输和缺氧诱导因子-1（HIF-1）信号通路相关的途径中。WGCNA分析产生的数据包含183个DEG。三种机器学习算法的应用确定了11个枢纽基因。在建立小鼠模型后，通过验证集进行的同步验证分析以及qPCR证实了BTBD10、内质网氨肽酶1（ERAP1）、GAIP相互作用蛋白C端（GIPC1）和过氧化物酶体生物发生因子6（PEX6）在CRSwNP中的过表达。免疫细胞浸润检查表明，CRSwNP组中2型辅助性T细胞和记忆B细胞的浸润率下降。相反，未成熟树突状细胞和效应记忆性CD8 T细胞的浸润率呈正相关。
本研究成功鉴定并验证了BTBD10、ERAP1、GIPC1和PEX6作为CRSwNP潜在的新型诊断或治疗靶点，为CRSwNP的诊断预测和治疗方法提供了新的视角和理论基础。
