DataSheet1_Transcriptomic analysis identifies the shared diagnostic biomarkers and immune relationship between Atherosclerosis and abdominal aortic aneurysm based on fatty acid metabolism gene set.docx

Background:Epidemiological research has demonstrated that there is a connection between lipid metabolism disorder and an increased risk of developing arteriosclerosis (AS) and abdominal aortic aneurysm (AAA). However, the precise relationship between lipid metabolism, AS, and AAA is still not fully understood. The objective of this study was to examine the pathways and potential fatty acid metabolism-related genes (FRGs) that are shared between AS and AAA.
Methods:AS- and AAA-associated datasets were retrieved from the Gene Expression Omnibus (GEO) database, and the limma package was utilized to identify differentially expressed FRGs (DFRGs) common to both AS and AAA patients. Functional enrichment analysis was conducted on the (DFRGs), and a protein-protein interaction (PPI) network was established. The selection of signature genes was performed through the utilization of least absolute shrinkage and selection operator (LASSO) regression and random forest (RF). Subsequently, a nomogram was developed using the results of the screening process, and the crucial genes were validated in two separate external datasets (GSE28829 and GSE17901) as well as clinical samples. In the end, single-sample gene set enrichment analysis (ssGSEA) was utilized to assess the immune cell patterns in both AS and AAA. Additionally, the correlation between key crosstalk genes and immune cell was evaluated.
Results:In comparison to control group, both AS and AAA patients exhibited a decrease in fatty acid metabolism score. We found 40 DFRGs overlapping in AS and AAA, with lipid and amino acid metabolism critical in their pathogenesis. PCBD1, ACADL, MGLL, BCKDHB, and IDH3G were identified as signature genes connecting AS and AAA. Their expression levels were confirmed in validation datasets and clinical samples. The analysis of immune infiltration showed that neutrophils, NK CD56dim cells, and Tem cells are important in AS and AAA development. Correlation analysis suggested that these signature genes may be involved in immune cell infiltration.
Conclusion:The fatty acid metabolism pathway appears to be linked to the development of both AS and AAA. Furthermore, PCBD1, ACADL, MGLL, BCKDHB, and IDH3G have the potential to serve as diagnostic markers for patients with AS complicated by AAA.

背景：流行病学研究证实，脂质代谢紊乱与动脉粥样硬化（arteriosclerosis, AS）、腹主动脉瘤（abdominal aortic aneurysm, AAA）的发病风险升高存在关联。然而，脂质代谢、动脉粥样硬化与腹主动脉瘤之间的确切关联仍未完全阐明。本研究旨在探究动脉粥样硬化与腹主动脉瘤共有的通路及潜在的脂肪酸代谢相关基因（fatty acid metabolism-related genes, FRGs）。
研究方法：从基因表达综合数据库（Gene Expression Omnibus, GEO）中检索动脉粥样硬化与腹主动脉瘤相关数据集，借助limma包筛选两类患者共有的差异表达脂肪酸代谢相关基因（differentially expressed FRGs, DFRGs）。对差异表达脂肪酸代谢相关基因进行功能富集分析，并构建蛋白质-蛋白质相互作用（protein-protein interaction, PPI）网络。通过最小绝对收缩和选择算子（least absolute shrinkage and selection operator, LASSO）回归与随机森林（random forest, RF）筛选特征基因。基于筛选结果构建列线图，并在两个独立外部数据集（GSE28829与GSE17901）及临床样本中验证关键基因。最后，采用单样本基因集富集分析（single-sample gene set enrichment analysis, ssGSEA）评估动脉粥样硬化与腹主动脉瘤的免疫细胞浸润模式，并分析关键互作基因与免疫细胞的相关性。
研究结果：与对照组相比，动脉粥样硬化与腹主动脉瘤患者的脂肪酸代谢评分均显著降低。本研究共筛选得到40个在动脉粥样硬化与腹主动脉瘤中重叠的差异表达脂肪酸代谢相关基因，其发病机制与脂质及氨基酸代谢密切相关。筛选得到PCBD1、ACADL、MGLL、BCKDHB及IDH3G作为连接动脉粥样硬化与腹主动脉瘤的特征基因，其表达水平在验证数据集与临床样本中均得到证实。免疫浸润分析显示，中性粒细胞、NK CD56dim细胞及Tem细胞在动脉粥样硬化与腹主动脉瘤的发生发展中发挥重要作用。相关性分析表明，上述特征基因可能参与免疫细胞浸润过程。
研究结论：脂肪酸代谢通路与动脉粥样硬化及腹主动脉瘤的发生发展密切相关。PCBD1、ACADL、MGLL、BCKDHB及IDH3G有望作为动脉粥样硬化合并腹主动脉瘤患者的诊断标志物。