中国全科医学2026，Vol.29Issue(18)：2523-2531,9.DOI:10.12114/j.issn.1007-9572.2025.0042
Stanford A型主动脉夹层病变关键基因筛选与免疫浸润研究
Screening of Hub Genes and Immune Infiltration Analysis in Stanford Type A Aortic Dissection
摘要
Abstract
Background Stanford type A aortic dissection(TAAD)is a life-threatening cardiovascular condition with high morbidity and mortality,requiring emergency surgical intervention.Due to the similarity of its clinical manifestations with other diseases such as acute coronary syndrome,diagnosis is often delayed.Identifying potential pathogenic genes of TAAD is crucial for early diagnosis and improving prognosis.Objective This study aims to identify hub pathogenic genes in TAAD through integrated bioinformatics analysis and experimental validation,and to explore their association with immune cell infiltration.Methods The GSE153434 dataset was downloaded from the gene expression omnibus(GEO)database.Differential expression analysis was performed using the Limma package in R.gene ontology(GO),disease ontology(DO),and KEGG enrichment analyses were conducted to elucidate the underlying molecular mechanisms of TAAD.Hub genes were screened and validated for expression consistency using the GSE52093 dataset.Receiver operating characteristic(ROC)curves were plotted to evaluate diagnostic performance.A TAAD model was established in 18 C57BL/6 mice via subcutaneous implantation of an angiotensinⅡ micro-osmotic pump.Aortic tissues were collected,and pathological changes were examined by hematoxylin and eosin(HE)staining.Quantitative real-time PCR(qPCR)was performed for validation.Immune cell infiltration differences and correlations were analyzed using the CIBERSORT algorithm.Results A total of 1 672 differentially expressed genes were identified in TAAD patients,including 1 064 upregulated and 608 downregulated genes.Functional enrichment analysis revealed their involvement in biological processes such as vascular system development,inflammatory response,and cytokine activity regulation,as well as key pathways including the PI3K-Akt and calcium signaling pathways.The TAAD model was successfully established in 10 out of 12 mice,with 4 mice dying due to aortic dissection.The remaining 6 mice were used for subsequent experiments.HE staining showed normal aortic wall structure and intact elastic fibers in the control(Con)group,whereas the aortic dissection(AD)group exhibited significant structural disruption,medial layer separation,elastic fiber fragmentation,and formation of true and false lumens with intraluminal thrombus.Validation via the GSE52093 dataset and mouse aortic qPCR indicated that secreted phosphoprotein 1(SPP1)may serve as a core gene in TAAD pathogenesis,with its expression correlated with infiltration of immune cells such as macrophages and T cells.Conclusion The pathogenesis of TAAD is closely associated with dysregulation of the PI3K-Akt and calcium signaling pathways,as well as immune microenvironment imbalance.SPP1 may serve as a potential biomarker and therapeutic target for TAAD,providing new research directions for early diagnosis and immunotherapy.Further multicenter clinical studies and molecular mechanism investigations are warranted to validate its clinical applicability.关键词
动脉瘤,夹层/Stanford A型主动脉夹层/枢纽基因/分泌性磷蛋白1/生物信息学分析/免疫浸润Key words
Aneurysm,dissecting/Stanford type A aortic dissection/Hub genes/Secreted phosphoprotein 1/Bioinformatics analysis/Immune infiltration分类
医药卫生引用本文复制引用
房彬彬,单春方,刘芬,田婷,谢骞,冀伟,李艳红,杨毅宁,李晓梅..Stanford A型主动脉夹层病变关键基因筛选与免疫浸润研究[J].中国全科医学,2026,29(18):2523-2531,9.基金项目
新疆维吾尔自治区天山英才培养计划(2023TSYCLJ0035) （2023TSYCLJ0035）
新疆维吾尔自治区自然科学基金重点项目(2022D01D22) （2022D01D22）
国家自然科学基金资助项目(82460099) （82460099）
新疆维吾尔自治区自然科学基金(2022D01C258) （2022D01C258）
