Department of Nephropathy and Immunology, The Third Central Clinical College of Tianjin Medical University, No. 83 Jintang Road, Hedong District, Tianjin, 300170, China.
Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, The Third Central Hospital of Tianjin, Tianjin, China.
Sci Rep. 2023 Jul 26;13(1):12126. doi: 10.1038/s41598-023-39012-w.
The diagnosis and assessment of ulcerative colitis (UC) poses significant challenges, which may result in inadequate treatment and a poor prognosis for patients. This study aims to identify potential activity biomarkers for UC and investigate the role of infiltrating immune cells in the disease. To perform gene set enrichment analysis, we utilized the cluster profiler and ggplot2 packages. Kyoto encyclopedia of genes and genomes was used to analyze degenerate enrichment genes. Significant gene set enrichment was determined using the cluster profiler and ggplot2 packages. Additionally, quantitative PCR (qRT-PCR) was employed to validate the expression of each marker in the ulcerative colitis model. We identified 651 differentially expressed genes (DEGs) and further investigated potential UC activity biomarkers. Our analysis revealed that CXCL1 (AUC = 0.710), CYP2R1 (AUC = 0.863), LPCAT1 (AUC = 0.783), and NEU4 (AUC = 0.833) were promising activity markers for the diagnosis of UC. Using rat DSS model, we validated these markers through qRT-PCR, which showed statistically significant differences between UC and normal colon mucosa. Infiltrating immune cell analysis indicated that M1 macrophages, M2 macrophages, activated dendritic cells (DCs), and neutrophils played crucial roles in the occurrence and progression of UC. Moreover, the activity markers exhibited varying degrees of correlation with activated memory CD4 T cells, M0 macrophages, T follicular helper cells, memory B cells, and activated DCs. The potential diagnostic genes for UC activity, such as CXCL1, CYP2R1, LPCAT1, and NEU4, as well as the infiltration of immune cells, may contribute to the pathogenesis and progression of UC.
溃疡性结肠炎(UC)的诊断和评估存在重大挑战,这可能导致患者治疗不足和预后不良。本研究旨在确定 UC 的潜在活性生物标志物,并研究浸润免疫细胞在疾病中的作用。为了进行基因集富集分析,我们使用了 cluster profiler 和 ggplot2 软件包。京都基因与基因组百科全书用于分析退化富集基因。使用 cluster profiler 和 ggplot2 软件包确定显著的基因集富集。此外,还采用定量 PCR(qRT-PCR)验证溃疡性结肠炎模型中每个标志物的表达。我们确定了 651 个差异表达基因(DEGs),并进一步研究了潜在的 UC 活性生物标志物。我们的分析表明,CXCL1(AUC=0.710)、CYP2R1(AUC=0.863)、LPCAT1(AUC=0.783)和 NEU4(AUC=0.833)是 UC 诊断的有前途的活性标志物。我们使用大鼠 DSS 模型通过 qRT-PCR 验证了这些标志物,结果显示 UC 与正常结肠黏膜之间存在统计学显著差异。浸润免疫细胞分析表明,M1 巨噬细胞、M2 巨噬细胞、活化树突状细胞(DC)和中性粒细胞在 UC 的发生和发展中起关键作用。此外,活性标志物与活化记忆 CD4 T 细胞、M0 巨噬细胞、滤泡辅助性 T 细胞、记忆 B 细胞和活化 DC 之间存在不同程度的相关性。用于 UC 活性的潜在诊断基因,如 CXCL1、CYP2R1、LPCAT1 和 NEU4,以及免疫细胞的浸润,可能有助于 UC 的发病机制和进展。