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Regulation mechanisms of disulfidptosis-related genes in ankylosing spondylitis and inflammatory bowel disease.
Li, Lin; Fang, Haixin; Li, Fuzhen; Xie, Kunpeng; Zhou, Pengyi; Zhu, Haiyan; Jin, Xuemin; Song, Ruifeng; Yang, Peizeng; Liping, Du.
Afiliación
  • Li L; 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.
  • Fang H; 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.
  • Li F; The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
  • Xie K; 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.
  • Zhou P; 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.
  • Zhu H; 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.
  • Jin X; 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.
  • Song R; 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.
  • Yang P; Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
  • Liping D; Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Front Immunol ; 15: 1326354, 2024.
Article en En | MEDLINE | ID: mdl-38433839
ABSTRACT

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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Espondilitis Anquilosante / Enfermedades Inflamatorias del Intestino / Colitis Ulcerosa / Enfermedad de Crohn Límite: Humans Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Espondilitis Anquilosante / Enfermedades Inflamatorias del Intestino / Colitis Ulcerosa / Enfermedad de Crohn Límite: Humans Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza