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Identification of Biomarkers, Pathways, Immune Properties of Mitophagy Genes, and Prediction Models for Intervertebral Disc Degeneration.
Huang, Yongxiong; Qiu, Xianshuai; Liu, Jinlian; Wan, Jiangtao; Yu, Cheng; Liu, Chun; Duan, Yang; Chen, Chong; Dai, Jingxing; Ouyang, Jun; Liu, Ming; Min, Shaoxiong; Qiu, Sujun.
Afiliación
  • Huang Y; Department of Spine Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People's Republic of China.
  • Qiu X; Department of Spine Surgery, Guangdong Provincial People's Hospital, Southern Medical University, Guangzhou, 510000, People's Republic of China.
  • Liu J; Department of Orthopedics and Sports Medicine Center, Heyou Hospital, Foshan, 528333, People's Republic of China.
  • Wan J; Department of Pathophysiology, Guangdong Provincial Key Laboratory of Shock and Microcirculation, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People's Republic of China.
  • Yu C; Shenzhen Key Laboratory of Spine Surgery, Department of Spine Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, People's Republic of China.
  • Liu C; Department of Spine Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People's Republic of China.
  • Duan Y; Department of Spine Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People's Republic of China.
  • Chen C; Department of Spine Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People's Republic of China.
  • Dai J; Department of Spine Surgery, Guangdong Provincial People's Hospital, Southern Medical University, Guangzhou, 510000, People's Republic of China.
  • Ouyang J; Guangdong Provincial Key Laboratory of Medical Biomechanics & National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People's Republic of China.
  • Liu M; Guangdong Provincial Key Laboratory of Medical Biomechanics & National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People's Republic of China.
  • Min S; Department of Orthopedics and Sports Medicine Center, Heyou Hospital, Foshan, 528333, People's Republic of China.
  • Qiu S; Department of Spine Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, People's Republic of China.
J Inflamm Res ; 17: 2959-2975, 2024.
Article en En | MEDLINE | ID: mdl-38764497
ABSTRACT

Background:

Intervertebral disc degeneration (IDD) is the leading cause of low back pain (LBP). The mechanism of IDD development and progression is not fully understood. Peripheral biomarkers are increasingly vital non-radioactive methods in early detection and diagnosis for IDD. Nevertheless, less attention has been paid to the role of mitophagy genes in the progress of IDD. This study aimed to identify the mitophagy disease-causing genes in the process of IDD and mitophagy diagnostic biomarkers for IDD.

Methods:

Mitophagy-related differentially expressed genes (MRDEGs) related to IDD were investigated by analyzing the microarray datasets of IDD cases from GEO, PathCards and Molecular Signatures Databases. We used R software, WGCNA, PPI, mRNA-miRNA, mRNA-TF, GO, KEGG, GSEA, GSVA and Cytoscape to analyze and visualize the data. We further used ssGSEA for immunoinfiltration analysis to obtain different immune cell infiltration. LASSO model was developed to screen for genes that met the diagnostic gene model requirements. Finally, qRT-PCR, Western blotting and HE were used to verify hub genes and their expression from clinical IDD samples.

Results:

We identified 14 MRDEGs and 12 hub genes. GO, KEGG, GSEA and GSVA analyses demonstrated that hub genes were critical for the development of IDD. LASSO diagnostic model consisted of six hub genes, among which SQSTM1, ATG7 and OPTN were significantly different between the two IDD disease subtypes. At the same time, SQSTM1 also had a high correlation with immune characteristic subtypes. The results of qRT-PCR and Western blotting also indicated that these genes were significantly differentially expressed in nucleus pulposus cells (NPCs) of the IDD group.

Conclusion:

We explored an association between MRDEGs-associated signature in IDD and validated that hub genes like SQSTM1 might serve as biomarkers for diagnostic and therapeutic targets for IDD. Meanwhile, this study can provide new insights into the functional characteristics and mechanism of mitophagy in the development of IDD.
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Inflamm Res Año: 2024 Tipo del documento: Article Pais de publicación: Nueva Zelanda

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Inflamm Res Año: 2024 Tipo del documento: Article Pais de publicación: Nueva Zelanda