通过综合生物信息学分析鉴定绝经后骨质疏松症中差异表达的基因、信号通路和免疫浸润
Identification of differentially expressed genes, signaling pathways and immune infiltration in postmenopausal osteoporosis by integrated bioinformatics analysis.
作者信息
Zhou Xiaoli, Chen Yang, Zhang Zepei, Miao Jun, Chen Guangdong, Qian Zhiyong
机构信息
Department of Spine Surgery, Tianjin Hospital, Tianjin University, Tianjin 300211, China.
Department of Toxicology, Tianjin Centers for Disease Control and Prevention, Tianjin 300011, China.
出版信息
Heliyon. 2023 Dec 16;10(1):e23794. doi: 10.1016/j.heliyon.2023.e23794. eCollection 2024 Jan 15.
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.
背景
绝经后骨质疏松症是一种全身性代谢紊乱疾病，其特征是骨转换失衡，骨吸收超过骨形成。这种失衡主要源于雌激素缺乏导致的骨量下降，以及骨微结构退化导致的骨折风险升高。尽管认识到了这些变化，但确切的致病因素和潜在的分子途径仍然难以捉摸。在本研究中，我们旨在通过综合生物信息学方法识别骨质疏松症中差异表达基因（DEGs）、相关途径以及免疫浸润的作用，以揭示潜在的分子机制。
方法
我们从基因表达综合数据库中检索了GSE230665的表达谱，其中包括15个股骨样本，包括12个绝经后骨质疏松症样本和3个正常对照。从汇总的微阵列数据集中，我们获得差异表达基因（DEGs）以进行进一步的生物信息学分析。我们使用加权基因共表达网络分析（WGCNA），分析DEGs、蛋白质-蛋白质相互作用（PPI），并进行基因本体（GO）分析以识别关键基因。然后我们使用CIBERSORT方法探索绝经后骨质疏松症影响的股骨标本中免疫细胞浸润的程度。为了探究关键基因与浸润免疫细胞之间的关系，我们进行了相关性分析。
结果
我们共鉴定出12204个DEGs。其中，12157个上调，47个下调。GO和京都基因与基因组百科全书（KEGG）途径分析表明这些DEGs主要靶向细胞蛋白质定位活性和相关信号通路。蛋白质-蛋白质相互作用网络突出了四个核心枢纽基因：核糖体蛋白L31（RPL31）、核糖体蛋白L34（RPL34）、真核生物延伸因子1γ（EEF1G）和溴结构域和含PHD结构域的转录因子（BPTF）。主成分分析表明这些基因的表达与静息自然杀伤（NK）细胞（根据CIBERSORT）呈正相关。相反，RPL31、RPL34和EEF1G的表达与T细胞（根据CIBERSORT的γδT细胞）呈负相关。
结论
免疫浸润在骨质疏松症的发展中起作用。
Zotero 插件