Table_1_The Integrated Analysis Identifies Three Critical Genes as Novel Diagnostic Biomarkers Involved in Immune Infiltration in Atherosclerosis.docx

Atherosclerosis (AS), a chronic inflammatory disease of the blood vessels, is the primary cause of cardiovascular disease, the leading cause of death worldwide. This study aimed to identify possible diagnostic markers for AS and determine their correlation with the infiltration of immune cells in AS. In total, 10 serum samples from AS patients and 10 samples from healthy subjects were collected. The original gene expression profiles of GSE43292 and GSE57691 were downloaded from the Gene Expression Omnibus database. Least absolute shrinkage and selection operator regression model and support vector machine recursive feature elimination analyses were carried out to identify candidate markers. The diagnostic values of the identified biomarkers were determined using receiver operating characteristic assays. The compositional patterns of the 22 types of immune cell fraction in AS were estimated using CIBERSORT. RT-PCR was performed to further determine the expression of the critical genes. This study identified 17 differentially expressed genes (DEGs) in AS samples. The identified DEGs were mainly involved in non-small cell lung carcinoma, pulmonary fibrosis, polycystic ovary syndrome, glucose intolerance, and T-cell leukemia. FHL5, IBSP, and SCRG1 have been identified as the diagnostic genes in AS. The expression of SCRG1 and FHL5 was distinctly downregulated in AS samples, and the expression of IBSP was distinctly upregulated in AS samples, which was further confirmed using our cohort by RT-PCR. Moreover, immune assays revealed that FHL5, IBSP, and SCRG1 were associated with several immune cells, such as CD8 T cells, naïve B cells, macrophage M0, activated memory CD4 T cells, and activated NK cells. Overall, future investigations into the occurrence and molecular mechanisms of AS may benefit from using the genes FHL5, IBSP, and SCRG1 as diagnostic markers for the condition.

动脉粥样硬化（AS），一种血管慢性炎症性疾病，是全球心血管疾病的首要病因，也是导致死亡的主要原因。本研究旨在识别动脉粥样硬化的可能诊断标志物，并确定其与免疫细胞浸润的相关性。共收集了10份动脉粥样硬化患者的血清样本和10份健康受试者的样本。从基因表达综合数据库中下载了GSE43292和GSE57691的原基因表达谱。采用最小绝对收缩和选择算子回归模型和支持向量机递归特征消除分析来识别候选标志物。使用受试者工作特征检验确定所识别生物标志物的诊断价值。利用CIBERSORT估计了动脉粥样硬化中22种免疫细胞亚群的组成模式。通过实时聚合酶链反应（RT-PCR）进一步确定关键基因的表达。本研究在动脉粥样硬化样本中确定了17个差异表达基因（DEGs）。所识别的DEGs主要涉及非小细胞肺癌、肺纤维化、多囊卵巢综合征、葡萄糖不耐症和T细胞白血病。FHL5、IBSP和SCRG1已被确认为动脉粥样硬化的诊断基因。在动脉粥样硬化样本中，SCRG1和FHL5的表达明显下调，而IBSP的表达明显上调，这一结果通过我们的队列研究进一步得到验证。此外，免疫学检测显示FHL5、IBSP和SCRG1与多种免疫细胞相关，如CD8 T细胞、未成熟B细胞、M0巨噬细胞、活化记忆CD4 T细胞和活化NK细胞。总体而言，未来对动脉粥样硬化的发生和分子机制的研究，可考虑利用FHL5、IBSP和SCRG1作为诊断标志物。