PDF(Pubmed)
Abstract：
UNASSIGNED: Chronic low-grade inflammation of the pancreatic islets is the characteristic of type 2 diabetes (T2D), and some of the immune checkpoints may play important roles in the pancreatic islet inflammation. Thus, we aim to explore the immune checkpoint genes (ICGs) associated with T2D, thereby revealing the role of ICGs in the pathogenesis of T2D based on bioinformatic analyses.
UNASSIGNED: Differentially expressed genes (DEGs) and immune checkpoint genes (ICGs) of islets between T2D and control group were screened from datasets of the Gene Expression Omnibus (GEO). A risk model was built based on the coefficients of ICGs calculated by ridge regression. Functional enrichment analysis and immune cell infiltration estimation were conducted. Correlations between ICGs and hub genes, T2D-related disease genes, insulin secretion genes, and beta cell function-related genes were analyzed. Finally, we conducted RT-PCR to verify the expression of these ICGs.
UNASSIGNED: In total, pancreatic islets from 19 cases of T2D and 84 healthy subjects were included. We identified 458 DEGs. Six significantly upregulated ICGs (CD44, CD47, HAVCR2, SIRPA, TNFSF9, and VTCN1) in T2D were screened out. These ICGs were significantly correlated with several hub genes and T2D-related genes; furthermore, they were correlated with insulin secretion and β cell function-related genes. The analysis of immune infiltration showed that the concentrations of eosinophils, T cells CD4 naive, and T cells regulatory (Tregs) were significantly higher, but CD4 memory resting T cells and monocytes were lower in islets of T2D patients. The infiltrated immune cells in T2D pancreatic islet were associated with these six ICGs. Finally, the expression levels of four ICGs were confirmed by RT-PCR, and three ICGs were validated in another independent dataset.
UNASSIGNED: In conclusion, the identified ICGs may play an important role in T2D. Identification of these differential genes may provide new clues for the diagnosis and treatment of T2D.
UNASSIGNED: Differentially expressed genes (DEGs) and immune checkpoint genes (ICGs) of islets between T2D and control group were screened from datasets of the Gene Expression Omnibus (GEO). A risk model was built based on the coefficients of ICGs calculated by ridge regression. Functional enrichment analysis and immune cell infiltration estimation were conducted. Correlations between ICGs and hub genes, T2D-related disease genes, insulin secretion genes, and beta cell function-related genes were analyzed. Finally, we conducted RT-PCR to verify the expression of these ICGs.
UNASSIGNED: In total, pancreatic islets from 19 cases of T2D and 84 healthy subjects were included. We identified 458 DEGs. Six significantly upregulated ICGs (CD44, CD47, HAVCR2, SIRPA, TNFSF9, and VTCN1) in T2D were screened out. These ICGs were significantly correlated with several hub genes and T2D-related genes; furthermore, they were correlated with insulin secretion and β cell function-related genes. The analysis of immune infiltration showed that the concentrations of eosinophils, T cells CD4 naive, and T cells regulatory (Tregs) were significantly higher, but CD4 memory resting T cells and monocytes were lower in islets of T2D patients. The infiltrated immune cells in T2D pancreatic islet were associated with these six ICGs. Finally, the expression levels of four ICGs were confirmed by RT-PCR, and three ICGs were validated in another independent dataset.
UNASSIGNED: In conclusion, the identified ICGs may play an important role in T2D. Identification of these differential genes may provide new clues for the diagnosis and treatment of T2D.
摘要：
■胰岛的慢性低度炎症是2型糖尿病（T2D）的特征，一些免疫检查点可能在胰岛炎症中起重要作用。因此，我们旨在探索与T2D相关的免疫检查点基因(ICGs)，从而基于生物信息学分析揭示ICGs在T2D发病机理中的作用。
■从基因表达综合（GEO）的数据集筛选T2D和对照组之间胰岛的差异表达基因（DEGs）和免疫检查点基因（ICGs）。基于岭回归计算的ICG系数，建立了风险模型。进行功能富集分析和免疫细胞浸润评估。ICGs和hub基因之间的相关性，T2D相关疾病基因,胰岛素分泌基因，并对β细胞功能相关基因进行分析。最后,我们进行了RT-PCR来验证这些ICGs的表达。
■总共，纳入19例T2D患者和84例健康受试者的胰岛。我们确定了458个DEG。六个显著上调的ICGs(CD44，CD47，HAVCR2，SIRPA，筛选出T2D中的TNFSF9和VTCN1)。这些ICGs与几个hub基因和T2D相关基因显着相关；此外，它们与胰岛素分泌和β细胞功能相关基因相关。免疫浸润分析表明,嗜酸性粒细胞的浓度,T细胞CD4幼稚，而调节性T细胞（Tregs）明显更高，但CD4记忆静息T细胞和单核细胞在T2D患者胰岛中较低。T2D胰岛中浸润的免疫细胞与这六个ICGs有关。最后,4种ICGs的表达水平经RT-PCR证实,三个ICG在另一个独立的数据集中进行了验证。
■总而言之，已识别的ICG可能在T2D中起重要作用。这些差异基因的鉴定可能为T2D的诊断和治疗提供新的线索。
■从基因表达综合（GEO）的数据集筛选T2D和对照组之间胰岛的差异表达基因（DEGs）和免疫检查点基因（ICGs）。基于岭回归计算的ICG系数，建立了风险模型。进行功能富集分析和免疫细胞浸润评估。ICGs和hub基因之间的相关性，T2D相关疾病基因,胰岛素分泌基因，并对β细胞功能相关基因进行分析。最后,我们进行了RT-PCR来验证这些ICGs的表达。
■总共，纳入19例T2D患者和84例健康受试者的胰岛。我们确定了458个DEG。六个显著上调的ICGs(CD44，CD47，HAVCR2，SIRPA，筛选出T2D中的TNFSF9和VTCN1)。这些ICGs与几个hub基因和T2D相关基因显着相关；此外，它们与胰岛素分泌和β细胞功能相关基因相关。免疫浸润分析表明,嗜酸性粒细胞的浓度,T细胞CD4幼稚，而调节性T细胞（Tregs）明显更高，但CD4记忆静息T细胞和单核细胞在T2D患者胰岛中较低。T2D胰岛中浸润的免疫细胞与这六个ICGs有关。最后,4种ICGs的表达水平经RT-PCR证实,三个ICG在另一个独立的数据集中进行了验证。
■总而言之，已识别的ICG可能在T2D中起重要作用。这些差异基因的鉴定可能为T2D的诊断和治疗提供新的线索。
