Chinese Journal of Tissue Engineering Research ›› 2024, Vol. 28 ›› Issue (32): 5116-5121.doi: 10.12307/2024.544
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Lu Xiaoling1, Liu Bin1, Xu Bin1, 2
Received:
2023-08-21
Accepted:
2023-11-04
Online:
2024-11-18
Published:
2023-12-28
Contact:
Xu Bin, Chief physician, Doctoral supervisor, School of Basic Medicine, Anhui Medical University, Hefei 230000, Anhui Province, China; Department of Orthopedics, First Affiliated Hospital of Anhui Medical University, Hefei 230000, Anhui Province, China
About author:
Lu Xiaoling, Master candidate, School of Basic Medicine, Anhui Medical University, Hefei 230000, Anhui Province, China
Supported by:
CLC Number:
Lu Xiaoling, Liu Bin, Xu Bin. Bioinformatics identification and validation of genes related to fatty acid metabolism in rheumatoid arthritis[J]. Chinese Journal of Tissue Engineering Research, 2024, 28(32): 5116-5121.
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2.1 内部数据集中差异表达基因的鉴定 将来自数据集GSE55235和GSE55457的微阵列数据组合作为内部数据集,包括20个正常样本和23个类风湿关节炎样本,检测到361个差异表达基因,其中249个上调,112个下调(图1A)。用STRING数据库构建一个由已识别的差异表达基因组成的蛋白质-蛋白质相互作用网络,使用Cytoscape软件中的MCC模式,筛选得分前75的基因(图1B),颜色越深代表联系越密切,由图可知CD8A和PTPRC这2个基因联系最为紧密。使用GO和KEGG富集分析差异表达基因功能,采用生物过程、细胞成分和分子功能3种方法来描述GO分析。生物过程结果显示差异表达基因主要富集与免疫反应相关的生物活性(图2A),细胞成分结果显示差异表达基因主要是质膜和免疫突触(图2B),分子功能结果显示差异表达基因与蛋白质结合和趋化因子受体结合密切相关(图2C)。KEGG结果表明,差异表达基因富含细胞因子-细胞因子受体相互作用和趋化因子信号通路(图2D)。"
2.2 选择特征基因 从MSigDB数据库中收集464个脂肪酸代谢相关基因。韦恩图显示MsigDB的脂肪酸代谢相关基因与类风湿关节炎差异表达基因的交叉点共有13个(图3A)。通过LASSO算法筛选出13个对类风湿关节炎有很大影响的脂肪酸代谢基因中鉴定了9个特征基因(图3B,C)。使用SVM-RFE算法鉴定5个基因为类风湿关节炎的诊断标志物(图3D)。交叉后,最终鉴定出5个共同的特征基因,即PCK1、PDK1、PTGS2、PLA2G2D、DPEP2(图3E)。结果发现与正常组样本相比,类风湿关节炎患者PDK1、PLA2G2D和DPEP2表达升高,PCK1和PTGS2表达降低(图3F)。进一步研究5个基因特征的ROC,以预测5个特征基因诊断类风湿关节炎疾病的准确性。特征基因ROC曲线的曲线下面积值DPEP2为0.736(图4A),PCK1为0.813(图4B),PDK1为0.766(图4C),PLA2G2D为0.838(图4D),PTGS2为0.812(图4E)。结果显示,5个基因特征具有相当好的预测效果。"
2.3 脂肪酸代谢相关基因与免疫的关系 CIBERSORT算法用于确定两组样本之间不同免疫细胞浸润水平的差异,通过堆叠直方图显示每个样本中22种免疫细胞类型的丰度分布(图5A),不同的颜色代表不同类型的免疫细胞,每种颜色的高度表示样品中细胞的百分比,百分比之和为1。箱式图中红色代表正常样本,蓝色代表类风湿关节炎样本(图5B),结果显示类风湿关节炎滑膜通常含有更高比例的静息肥大细胞(P < 0.01)和中性粒细胞(P < 0.05),而正常滑膜含有更高比率的记忆性静息CD4+ T细胞(P < 0.05)和活化肥大细胞(P < 0.01)。同时计算免疫细胞含量与脂肪酸代谢相关基因之间的相关性,结果表明DPEP2(r=-0.55,P=0.000 12)、PDK1(r=-0.41,P=0.006 5)、PLA2G2D(r=-0.52,P=0.000 038)与活化的肥大细胞呈负相关;PTGS2与活化肥大细胞呈正相关(r=0.62,P=7.5×10-6);DPEP2与静息肥大细胞正相关(r=0.4,P=0.007 9),与记忆性静息CD4+ T细胞(r=0.51,P=0.000 55)呈负相关;PDK1与记忆性静息CD4+ T细胞呈负相关(r=-0.46,P=0.002 2),见图5C-K。这些结果表明特征基因与类风湿关节炎患者的免疫细胞浸润水平密切相关。"
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