对自噬相关基因表达谱进行综合分析，确定了与颈动脉粥样硬化中免疫浸润和进展斑块相关的五个基因生物标志物。
Comprehensive analysis of autophagy-related gene expression profiles identified five gene biomarkers associated with immune infiltration and advanced plaques in carotid atherosclerosis.
机构信息
Department of Cerebrovascular Disease, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China.
Henan Provincial NeuroInterventional Engineering Research Center, Henan International Joint Laboratory of Cerebrovascular Disease, and Henan Engineering Research Center of Cerebrovascular Intervention Innovation, Zhengzhou, Henan, 450003, China.
出版信息
Orphanet J Rare Dis. 2023 Mar 23;18(1):66. doi: 10.1186/s13023-023-02660-2.
BACKGROUND
Autophagy plays an important role in the progression of carotid atherosclerosis (CAS). This study aimed to identify hub autophagy-related genes (ATGs) associated with CAS.
METHODS
GSE43292 and GSE28829 datasets of early and advanced CAS plaques were enrolled from the Gene Expression Omnibus (GEO) database. A comprehensive analysis of differentially expressed ATGs (DE-ATGs) was conducted. Functional enrichment assay was used to explore biological functions of DE-ATGs. The hub ATGs were identified by protein-protein interaction (PPI) network. Immunohistochemistry (IHC) and Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to validate hub ATGs at the protein level and mRNA level. Correlation analysis of hub ATGs with immune cells was also conducted. In addition, a competitive endogenous RNA (ceRNA) network was constructed, and diagnostic value of hub ATGs was evaluated.
RESULTS
A total of 19 DE-ATGs were identified in early and advanced CAS plaques. Functional enrichment analysis of DE-ATGs suggested that they were closely correlated to autophagy, apoptosis, and lipid regulation. Moreover, 5 hub ATGs, including TNFSF10, ITGA6, CTSD, CCL2, and CASP1, were identified and further verified by IHC. The area under the curve (AUC) values of the 5 hub ATGs were 0.818, 0.732, 0.792, 0.814, and 0.812, respectively. Competing endogenous RNA (ceRNA) networks targeting the hub ATGs were also constructed. In addition, the 5 hub ATGs were found to be closely associated with immune cell infiltration in CAS.
CONCLUSION
In this study, we identified 5 hub ATGs including CASP1, CCL2, CTSD, ITGA6 and TNFSF10, which could serve as candidate diagnostic biomarkers and therapeutic targets.
背景
自噬在颈动脉粥样硬化（CAS）的进展中起着重要作用。本研究旨在鉴定与 CAS 相关的关键自噬相关基因（ATG）。
方法
从基因表达综合（GEO）数据库中招募了早期和晚期 CAS 斑块的 GSE43292 和 GSE28829 数据集。对差异表达的 ATG（DE-ATG）进行了全面分析。功能富集分析用于探索 DE-ATG 的生物学功能。通过蛋白质-蛋白质相互作用（PPI）网络鉴定关键 ATG。免疫组织化学（IHC）和实时逆转录定量聚合酶链反应（RT-qPCR）用于在蛋白质水平和 mRNA 水平验证关键 ATG。还进行了关键 ATG 与免疫细胞相关性的分析。此外，构建了竞争性内源性 RNA（ceRNA）网络，并评估了关键 ATG 的诊断价值。
结果
在早期和晚期 CAS 斑块中鉴定出 19 个差异表达的 ATG。DE-ATG 的功能富集分析表明，它们与自噬、凋亡和脂质调节密切相关。此外，通过 IHC 进一步验证了 5 个关键 ATG，包括 TNFSF10、ITGA6、CTSD、CCL2 和 CASP1。这 5 个关键 ATG 的曲线下面积（AUC）值分别为 0.818、0.732、0.792、0.814 和 0.812。针对关键 ATG 的竞争性内源性 RNA（ceRNA）网络也被构建。此外，还发现这 5 个关键 ATG 与 CAS 中的免疫细胞浸润密切相关。
结论
在这项研究中，我们鉴定了 5 个关键 ATG，包括 CASP1、CCL2、CTSD、ITGA6 和 TNFSF10，它们可以作为候选诊断生物标志物和治疗靶点。
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