Integrative analysis of cellular autophagy-related genes in steroid-induced osteonecrosis of the femoral head

Yu Wang; Yuke Zhang; Hongxu Lu; Kai Liu; Wanxiong He; Zhiwei Pei; Jianzhong Wang

Integrative analysis of cellular autophagy-related genes in steroid-induced osteonecrosis of the femoral head

Am J Transl Res. 2023 Sep 15;15(9):5850-5872. eCollection 2023.

Authors

Yu Wang¹, Yuke Zhang¹, Hongxu Lu¹, Kai Liu¹, Wanxiong He¹, Zhiwei Pei¹, Jianzhong Wang²

Affiliations

¹ Inner Mongolia Medical University Hohhot 010050, Inner Mongolia, China.
² Department of Orthopedics and Traumatology, The Second Affiliated Hospital of Inner Mongolia Medical University Hohhot 010030, Inner Mongolia, China.

PMID: 37854226
PMCID: PMC10579027

Abstract

Objective: This study aimed to identify and evaluate genes associated with cellular autophagy in steroid hormonal femoral head necrosis.

Methods: Autophagy-related differentially expressed genes (ARDEGs) in steroid-induced osteonecrosis of the femoral head (SONFH) were identified by obtaining the intersection of differentially expressed genes (DEGs) and autophagy-related genes in a SONFH Gene Expression Omnibus dataset. The ARDEGs were screened, and correlations between gene expression and immune cell infiltration were evaluated. Finally, the validation of hub genes was undertaken through quantitative real-time-PCR.

Results: A comparison of peripheral blood samples from patients with and without SONFH revealed 189 DEGs. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analyses showed that the DEGs were related to various biologic processes (e.g., neutrophil activation) and pathways (e.g., hematopoietic cell lineage). The expression levels of these genes were correlated with the infiltration of multiple immune cell types. Among the 189 putative autophagy-related genes associated with SONFH, three genes, RPL6, RPL9, and RPL23, were identified as candidate biomarkers or therapeutic targets based on network analysis and their correlations with immune cell subtypes. The quantitative real-time polymerase chain reaction results confirmed our prediction regarding the mRNA expression of RPL9 and RPS6.

Conclusion: In this study, we identified 189 putative autophagy-related genes associated with SONFH, and the prediction of down-regulated genes RPL9 and RPS6 was validated using PCR, thereby expanding our understanding of the contribution of autophagy to SONFH.

Keywords: Steroid-induced osteonecrosis; autophagy; femoral head; integrative analysis; qRT-PCR.