Orphanet Journal of Rare Diseases (Mar 2023)

Comprehensive analysis of autophagy-related gene expression profiles identified five gene biomarkers associated with immune infiltration and advanced plaques in carotid atherosclerosis

  • Chi Ma,
  • Taoyuan Lu,
  • Yanyan He,
  • Dehua Guo,
  • Lin Duan,
  • Rufeng Jia,
  • Dongyang Cai,
  • Tao Gao,
  • Zhongcan Chen,
  • Binghua Xue,
  • Tianxiao Li,
  • Yingkun He

DOI
https://doi.org/10.1186/s13023-023-02660-2
Journal volume & issue
Vol. 18, no. 1
pp. 1 – 15

Abstract

Read online

Abstract 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.

Keywords