Tu Haixia, Fang Changjiang, Gan Ping, Gu Yunyun, Peng Nana, Jiang Honghua, Hou Weiwei, Shu Guihua
Department of Neonatology, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
Department of Pediatrics, The First People's Hospital of Kunshan, Suzhou, China.
Front Pediatr. 2025 Jul 15;13:1578628. doi: 10.3389/fped.2025.1578628. eCollection 2025.
Bronchopulmonary dysplasia (BPD) is the most common serious complication in very preterm infants. This study aims to identify necroptosis-related genes (NRGs) and analyze the relationship between necroptosis-related diagnostic markers and immune infiltration in BPD.
We obtained the dataset GSE32472 from the GEO database and analyzed the differentially expressed NRGs (DE-NRGs). We identified the biological functions and pathways of DE-NRGs. RF (random forest) and LASSO (least absolute shrinkage and selection operator) algorithms were applied to identify hub genes. We explored the immune landscape of BPD and controls by CIBERSORT. The correlations between hub genes and immune cells were evaluated using Spearman correlation analysis. ELISA was used to verify the diagnostic value of hub genes in patients with BPD in our hospital.
27 DE-NRGs were screened. We found the primary biological functions and pathways of DE-NRGs, including necroptosis, and regulation of inflammatory response. Three hub genes (PELI1, PYGL, and STAT4) were identified and utilized to construct a diagnostic nomogram. The AUC value of the nomogram was greater than 0.7 in the validation dataset GSE188944. CIBERSORT showed that the proportions of 6 different immune cell types in the BPD group were higher or lower than the control group ( < 0.05). Correlation analysis showed that three hub genes may correlate with immune cells to varying degrees. Serum ELISA results of PELI1 and PYGL showed no significant difference between BPD and Controls ( > 0.05), the expression level of STAT4 was downregulated in BPD samples ( < 0.05), and the AUC value of the STAT4 was higher than 0.7.
The necroptosis-related gene STAT4 can be a diagnostic marker of BPD patients. The necroptosis-related gene and immune infiltration may be related to the progression of BPD.
支气管肺发育不良（BPD）是极早产儿最常见的严重并发症。本研究旨在鉴定坏死性凋亡相关基因（NRGs），并分析坏死性凋亡相关诊断标志物与BPD中免疫浸润之间的关系。
我们从GEO数据库获得数据集GSE32472，并分析差异表达的NRGs（DE-NRGs）。我们确定了DE-NRGs的生物学功能和途径。应用随机森林（RF）和最小绝对收缩和选择算子（LASSO）算法鉴定枢纽基因。我们通过CIBERSORT探索BPD和对照组的免疫格局。使用Spearman相关分析评估枢纽基因与免疫细胞之间的相关性。采用酶联免疫吸附测定（ELISA）验证我院BPD患者中枢纽基因的诊断价值。
筛选出27个DE-NRGs。我们发现了DE-NRGs的主要生物学功能和途径，包括坏死性凋亡和炎症反应调节。鉴定出三个枢纽基因（PELI1、PYGL和STAT4）并用于构建诊断列线图。在验证数据集GSE188944中，列线图的曲线下面积（AUC）值大于0.7。CIBERSORT显示，BPD组中6种不同免疫细胞类型的比例高于或低于对照组（< 0.05）。相关分析表明，三个枢纽基因可能与免疫细胞存在不同程度的相关性。PELI1和PYGL的血清ELISA结果显示BPD组和对照组之间无显著差异（> 0.05），BPD样本中STAT4的表达水平下调（< 0.05），且STAT4的AUC值高于0.7。
坏死性凋亡相关基因STAT4可作为BPD患者的诊断标志物。坏死性凋亡相关基因和免疫浸润可能与BPD的进展有关。
