Wang Houyuan, Xiao JiaCong, Fu Caixia, Ma JIzhi, Jiang Ziwei
The First Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.
Guangzhou University of Chinese Medicine, Guangzhou, China.
Sci Rep. 2025 Aug 11;15(1):29387. doi: 10.1038/s41598-025-15227-x.
The co-occurrence of osteoporosis (OP) and type 1 diabetes mellitus (T1DM) represents a clinically significant comorbidity pattern, characterized by skeletal fragility and insulin deficiency. While epidemiological links exist, their shared molecular mechanisms remain undefined. This study investigates autophagy-a critical cellular degradation pathway-as a potential mechanistic bridge between OP and T1DM pathogenesis. We integrated multi-omics approaches using GEO datasets to identify autophagy- associated hub genes. Machine learning (LASSO/Random Forest) prioritized CPNE1 and FRAT2, validated through ROC curve analysis. Functional annotation via GO/KEGG enrichment analyses revealed enrichment in disease-associated pathways, corroborated by immune infiltration profiling and single-cell RNA sequencing showing cell-type-specific expression patterns. miRNA-gene regulatory networks further elucidated post-transcriptional control mechanisms. Our integrated analyses suggest that CPNE1 and FRAT2 may represent novel targets for combined diagnosis and therapy in OP and T1DM, where autophagic dysregulation could contribute to comorbid pathogenesis. These insights offer fresh perspectives for developing dual-disease management approaches.
骨质疏松症(OP)与1型糖尿病(T1DM)的共病是一种具有临床意义的合并症模式,其特征为骨骼脆弱和胰岛素缺乏。虽然存在流行病学关联,但其共同的分子机制仍不明确。本研究调查自噬(一种关键的细胞降解途径)作为OP和T1DM发病机制之间潜在的机制桥梁。我们使用GEO数据集整合多组学方法来识别自噬相关的枢纽基因。机器学习(LASSO/随机森林)将CPNE1和FRAT2列为优先对象,并通过ROC曲线分析进行了验证。通过GO/KEGG富集分析进行的功能注释揭示了在疾病相关途径中的富集,免疫浸润分析和单细胞RNA测序证实了细胞类型特异性表达模式。miRNA-基因调控网络进一步阐明了转录后控制机制。我们的综合分析表明,CPNE1和FRAT2可能代表OP和T1DM联合诊断和治疗的新靶点,其中自噬失调可能导致共病发病机制。这些见解为开发双病管理方法提供了新的视角。