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. 2023 Dec 16;10(1):e23794.
doi: 10.1016/j.heliyon.2023.e23794. eCollection 2024 Jan 15.

Identification of differentially expressed genes, signaling pathways and immune infiltration in postmenopausal osteoporosis by integrated bioinformatics analysis

Xiaoli Zhou  1   2 , Yang Chen  1 , Zepei Zhang  1 , Jun Miao  1 , Guangdong Chen  3 , Zhiyong Qian  2
Affiliations

Identification of differentially expressed genes, signaling pathways and immune infiltration in postmenopausal osteoporosis by integrated bioinformatics analysis

Xiaoli Zhou et al. Heliyon. .

Abstract

Background: Postmenopausal osteoporosis is a systemic metabolic disorder typified by an imbalance in bone turnover, where bone resorption supersedes bone formation. This imbalance primarily arises from a decline in bone mass induced by estrogen deficiency, and an elevated risk of fractures resulting from degradation of bone microstructure. Despite recognizing these changes, the precise causative factors and potential molecular pathways remain elusive. In this study, we aimed to identify differentially expressed genes (DEGs), associated pathways, and the role of immune infiltration in osteoporosis, leveraging an integrated bioinformatics approach to shed light on potential underlying molecular mechanisms.

Methods: We retrieved the expression profiles of GSE230665 from the Gene Expression Omnibus database, comprising 15 femur samples, including 12 postmenopausal osteoporosis samples and 3 normal controls. From the aggregated microarray datasets, we derived differentially expressed genes (DEGs) for further bioinformatics analysis. We used WGCNA, analyzed DEGs, PPI, and conducted GO analysis to identify pivotal genes. We then used the CIBERSORT method to explore the degree of immune cell infiltration within femur specimens affected by postmenopausal osteoporosis. To probe into the relationship between pivotal genes and infiltrating immune cells, we conducted correlation analysis.

Results: We identified a total of 12,204 DEGs. Among these, 12,157 were up-regulated, and 47 were down-regulated. GO and KEGG pathway analyses indicated that these DEGs predominantly targeted cellular protein localization activity and associated signaling pathways. The protein-protein interaction network highlighted four central hub-genes: RPL31, RPL34, EEF1G, and BPTF. Principal component analysis indicated a positive correlation between the expression of these genes and resting NK cells (as per CIBERSORT). In contrast, the expression of RPL31, RPL34, and EEF1G showed a negative correlation with T cells (gamma delta per CIBERSORT).

Conclusions: Immune infiltration plays a role in the development of osteoporosis.

Keywords: Bioinformatics; Hub genes; Postmenopausal osteoporosis; WGCNA.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Workflow chart of the present study.
Fig. 2
Fig. 2
Expression profile of DEGs. A Volcano map of DEGs expression levels. B Heatmap of top 30 DEGs.
Fig. 3
Fig. 3
WGCNA of DEGs. A. Estimation of the soft thresholding value for a scale-free co-expression network. B.Cluster dendrogram of all DEGs. C. Correlation between each module and postmenopausal osteoporosis patients or controls.
Fig. 4
Fig. 4
Gene ontology and KEGG enrichment analysis. A. Biological process. B. Cellular component. C. Molecular function. D. KEGG enrichment analysis.
Fig. 5
Fig. 5
PPI network and hub gene. A. PPI network. B, C, D. The three most significant modules. E. The overlapped hub genes from different algorithms.
Fig. 6
Fig. 6
Putative RPL31,RPL34, and BPTF protein–protein interaction network and GO analysis A. PPI network. B. Biological process. C. Cellular component. D. Molecular function.
Fig. 7
Fig. 7
Immune cell infiltration analysis. A. Heat map of relative proportions of 22 infiltrated immune cells in patients with Postmenopausal osteoporosis. B. Violin chart of the abundance of each type of immune cell infiltration in Postmenopausal osteoporosis and control groups. C. The correlation analysis of hub-genes and NK_cells_resting_CIBERSORT, T_cells_gamma_delta_CIBERSORT in Postmenopausal osteoporosis.
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