Li Lin, Fang Haixin, Li Fuzhen, Xie Kunpeng, Zhou Pengyi, Zhu Haiyan, Jin Xuemin, Song Ruifeng, Yang Peizeng, Liping Du
Department of Ophthalmology, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury Repair, The First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Zhengzhou, Henan, China.
The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
Front Immunol. 2024 Feb 16;15:1326354. doi: 10.3389/fimmu.2024.1326354. eCollection 2024.
Disulfidptosis is a recently identified form of cell death that contributes to maintaining the internal environment balance of an organism. However, the molecular basis of disulfidptosis in ulcerative colitis (UC), ankylosing spondylitis (AS), and Crohn's disease (CD) has not been thoroughly explored.
Firstly, the differentially expressed genes (DEGs) and disulfidptosis-associated genes (DAGs) were obtained through differential analysis between diseases (AS, CD, and UC) and control groups. After the disulfidptosis score was acquired using the single-sample gene set enrichment analysis (ssGSEA) algorithm, the DE-DAGs were screened by overlapping DAGs and DEGs of the three diseases. Next, the feature genes were selected through a combination of machine learning algorithms, receiver operating characteristic (ROC) curves, and expression analysis. Based on these feature genes, nomograms were created for AS, CD and UC. The co-feature genes were then identified by taking the intersections of the genes featured in all three diseases. Meanwhile, single-gene set enrichment analysis (GSEA) and the TF-mRNA-miRNA network were utilized to investigate the molecular mechanisms of the co-feature genes. To validate the expression differences of the co-feature genes between healthy controls and patients (AS and IBD), RT-PCR was performed. Lastly, mendelian randomization (MR) analysis was utilized to explore the causality between genetic variants of with AS, UC and CD.
In this study, 11 DE-DAGs were obtained. Functional enrichment analysis revealed their involvement in cytokine production and fatty acid biosynthesis. Latterly, AS/CD/UC -feature genes were derived, and they all had decent diagnostic performance. Through evaluation, the performance of the nomogram was decent for three diseases. Then, 2 co-feature genes ( and ) were obtained. The GSEA enrichment results indicated that the co-feature genes were mainly enriched in the cytokine-cytokine receptor interaction and drug metabolism cytochrome P450. As shown by functional experiments, there was a correlation between the mRNA expression of with AS, UC and CD. Additionally, a causal connection between and IBD was detected through MR analysis.
In this study, 2 co-feature genes ( and ) were screened, and their functions were investigated in AS, CD and UC, providing a basis for further research into diagnosis and treatment.
二硫化物诱导的细胞死亡是最近发现的一种细胞死亡形式，有助于维持生物体的内环境平衡。然而，溃疡性结肠炎（UC）、强直性脊柱炎（AS）和克罗恩病（CD）中二硫化物诱导的细胞死亡的分子基础尚未得到充分探索。
首先，通过疾病（AS、CD和UC）与对照组之间的差异分析获得差异表达基因（DEG）和二硫化物诱导的细胞死亡相关基因（DAG）。使用单样本基因集富集分析（ssGSEA）算法获得二硫化物诱导的细胞死亡评分后，通过重叠三种疾病的DAG和DEG筛选出DE-DAG。接下来，通过机器学习算法、受试者工作特征（ROC）曲线和表达分析相结合的方式选择特征基因。基于这些特征基因，为AS、CD和UC创建列线图。然后通过取所有三种疾病中具有特征的基因的交集来鉴定共同特征基因。同时，利用单基因集富集分析（GSEA）和TF-mRNA-miRNA网络来研究共同特征基因的分子机制。为了验证健康对照与患者（AS和炎症性肠病（IBD））之间共同特征基因的表达差异，进行了逆转录聚合酶链反应（RT-PCR）。最后，利用孟德尔随机化（MR）分析来探索与AS、UC和CD的基因变异之间的因果关系。
在本研究中，获得了11个DE-DAG。功能富集分析表明它们参与细胞因子产生和脂肪酸生物合成。随后，得出了AS/CD/UC特征基因，它们都具有良好的诊断性能。通过评估，列线图对三种疾病的性能良好。然后，获得了2个共同特征基因（和）。GSEA富集结果表明，共同特征基因主要富集在细胞因子-细胞因子受体相互作用和药物代谢细胞色素P450中。功能实验表明，与AS、UC和CD的mRNA表达之间存在相关性。此外，通过MR分析检测到与IBD之间的因果关系。
在本研究中，筛选出了两个共同特征基因（和），并在AS、CD和UC中研究了它们的功能，为进一步的诊断和治疗研究提供了依据。
