Regulation mechanisms of disulfidptosis-related genes in ankylosing spondylitis and inflammatory bowel disease

作者全名："Li, Lin; Fang, Haixin; Li, Fuzhen; Xie, Kunpeng; Zhou, Pengyi; Zhu, Haiyan; Jin, Xuemin; Song, Ruifeng; Yang, Peizeng; Du, Liping"

作者地址："[Li, Lin; Fang, Haixin; Li, Fuzhen; Xie, Kunpeng; Zhou, Pengyi; Zhu, Haiyan; Jin, Xuemin; Du, Liping] Zhengzhou Univ, Henan Prov Eye Hosp, Dept Ophthalmol,Affiliated Hosp 1, Henan Int Joint Res Lab Ocular Immunol & Retinal I, Zhengzhou, Henan, Peoples R China; [Fang, Haixin] Zhengzhou Univ, Acad Med Sci, Zhengzhou, Peoples R China; [Song, Ruifeng] Zhengzhou Univ, Dept Gastroenterol, Affiliated Hosp 1, Zhengzhou, Henan, Peoples R China; [Yang, Peizeng] First Affiliated Hosp Chongqing Med Univ, Chongqing Key Lab Ophthalmol, Chongqing Key Lab Ophthalmol, Affiliated Hosp 1, Chongqing, Peoples R China; [Yang, Peizeng] First Affiliated Hosp Chongqing Med Univ, Chongqing Eye Inst, Chongqing, Peoples R China"

通信作者："Du, LP (通讯作者)，Zhengzhou Univ, Henan Prov Eye Hosp, Dept Ophthalmol,Affiliated Hosp 1, Henan Int Joint Res Lab Ocular Immunol & Retinal I, Zhengzhou, Henan, Peoples R China.; Song, RF (通讯作者)，Zhengzhou Univ, Dept Gastroenterol, Affiliated Hosp 1, Zhengzhou, Henan, Peoples R China.; Yang, PZ (通讯作者)，First Affiliated Hosp Chongqing Med Univ, Chongqing Key Lab Ophthalmol, Chongqing Key Lab Ophthalmol, Affiliated Hosp 1, Chongqing, Peoples R China.; Yang, PZ (通讯作者)，First Affiliated Hosp Chongqing Med Univ, Chongqing Eye Inst, Chongqing, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001174095200001

JCR分区：Q1

影响因子：7.3

年份：2024

卷号：15

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：bioinformatics; mendelian randomization; disulfidptosis; ankylosing spondylitis; ulcerative colitis; Crohn's disease

摘要："Introduction 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.Methods 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 S100A12 with AS, UC and CD.Results 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 (S100A12 and LILRA5) 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 S100A12 with AS, UC and CD. Additionally, a causal connection between S100A12 and IBD was detected through MR analysis.Discussion In this study, 2 co-feature genes (S100A12 and LILRA5) were screened, and their functions were investigated in AS, CD and UC, providing a basis for further research into diagnosis and treatment."

基金机构："National Natural Science Foundation of China [82301271, 81970792, 82171040, 82101108]; Medical Science and Technology Project of Health Commission of Henan Province [YXKC2020026]; Key Scientific Research Projects of Henan Province Colleges and Universities [23A320067]; Major Program of Medical Scientific and Technological of Henan Province (XXX); Medical Scientific and Technological Project of Henan Province [SBGJ2020003031]"

基金资助正文："The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by National Natural Science Foundation of China [82301271, 81970792, 82171040 and 82101108], Medical Science and Technology Project of Health Commission of Henan Province [YXKC2020026], Key Scientific Research Projects of Henan Province Colleges and Universities [23A320067], Major Program of Medical Scientific and Technological of Henan Province (XXX), Medical Scientific and Technological Project of Henan Province (SBGJ2020003031)."