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基于生物信息学的腹主动脉瘤脂质和免疫相关生物标志物的鉴定

Bioinformatics-based identification of lipid- and immune-related biomarkers in abdominal aortic aneurysms.

作者信息

Li Yuejin, Li Rougang, Guo Shikui, Li Yu, Wang Yongzhi, Wen Xin, Lan Tian, Gong Kunmei

机构信息

Department of General Surgery, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, China.

出版信息

Heliyon. 2023 Feb 10;9(2):e13622. doi: 10.1016/j.heliyon.2023.e13622. eCollection 2023 Feb.

Abstract

BACKGROUND

Abdominal aortic aneurysm (AAA) manifest as a natural inflammatory process with permanent dilation and terminal rupture. Nevertheless, the pathogenesis of AAA remains a mystery, and treatment is still controversial. Lipid metabolism and immune system are involved in AAA progression, which has been well documented. However, lipid- and immune-related (LIR) biomarkers need to be further elucidated.

METHODS

The AAA-related datasets were retrieved from the GEO database, and the datasets were analyzed for differential gene expression by NetworkAnalyst. GO and KEGG pathway enrichment analysis of differentially expressed mRNA (DE-mRNA) was performed using Metscape, and LIR DE-mRNA was further screened. AAA rat model was constructed using porcine pancreatic elastase to verify the differential expression of LIR DE-mRNA.

RESULTS

The GSE47472 and GSE57691 datasets respectively identified 614 (containing 381 down-regulated and 233 up-regulated DE-mRNAs) and 384 (containing 218 down-regulated and 164 up-regulated DE-mRNAs) DE-mRNAs. Intersection and union of DE-mRNAs were 13 and 983, respectively. The main terms involved in the union of DE-mRNAs included "immune system process", "metabolic process", "Chemokine signaling pathway", "hematopoietic cell lineage" and "Cholesterol metabolism". experiments revealed that LIR DE-mRNAs of PDIA3, TYROBP, and HSPA1A were significantly low expression in AAA abdominal aortic tissues, and HCK and SERPINE1 were significantly high expression, which is consistent with the bioinformatics analysis.

CONCLUSIONS

PDIA3, TYROBP, HSPA1A, HCK and SERPINE1 may serve as LIR biomarkers of AAA, which provides new insights and theoretical guidance for the future treatment, early prevention and progression of AAA.

摘要

背景

腹主动脉瘤(AAA)表现为一种伴有永久性扩张和最终破裂的自然炎症过程。然而,AAA的发病机制仍是一个谜,治疗方法仍存在争议。脂质代谢和免疫系统参与AAA的进展,这已得到充分证实。然而,脂质和免疫相关(LIR)生物标志物仍需进一步阐明。

方法

从GEO数据库中检索AAA相关数据集,并通过NetworkAnalyst对数据集进行差异基因表达分析。使用Metscape对差异表达mRNA(DE-mRNA)进行GO和KEGG通路富集分析,并进一步筛选LIR DE-mRNA。使用猪胰弹性蛋白酶构建AAA大鼠模型,以验证LIR DE-mRNA的差异表达。

结果

GSE47472和GSE57691数据集分别鉴定出614个(包括381个下调和233个上调的DE-mRNA)和384个(包括218个下调和164个上调的DE-mRNA)DE-mRNA。DE-mRNA的交集和并集分别为13个和983个。DE-mRNA并集中涉及的主要术语包括“免疫系统过程”、“代谢过程”、“趋化因子信号通路”、“造血细胞谱系”和“胆固醇代谢”。实验表明,PDIA3、TYROBP和HSPA1A的LIR DE-mRNA在AAA腹主动脉组织中显著低表达,而HCK和SERPINE1显著高表达,这与生物信息学分析一致。

结论

PDIA3、TYROBP、HSPA1A、HCK和SERPINE1可能作为AAA的LIR生物标志物,为AAA的未来治疗、早期预防和病情进展提供了新的见解和理论指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7611/9984436/22ed06133d24/gr1.jpg

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