背景:滑膜软骨瘤病(SC)主要影响主要关节,其特征是良性软骨结节的形成。在本研究中,我们评估了SC和正常软骨的组织学和基因表达的差异,并进一步阐明了SC中hub基因的功能。
方法:进行组织学染色和生化分析,以测量SC和正常软骨样品中的胶原蛋白和糖胺聚糖(GAG)含量。然后,使用膝关节样品(三个正常和三个SC样品)进行微阵列分析以鉴定差异表达的基因(DEGs)。随后,进行生物信息学分析以鉴定hub基因并探索SC的潜在机制。前10个上调DEG的交点,前10个下调的DEG,并在SC组织中验证了hub基因。最后,体外实验和我们的临床队列用于确定潜在的生物学功能和诊断价值,分别,最重要的基因。
结果:SC组织中的GAG和胶原蛋白含量与正常组织相当或更高。微阵列分析显示SC中143个上调和107个下调的DEG。此外,功能富集分析显示免疫和代谢相关途径与SC发育之间存在关联。在20个枢纽基因中,两个交叉基因,即,胶原III型α1链(COL3A1)和HSPA8在SC组织中显著表达,与COL3A1表现出更显著的mRNA表达差异。此外,COL3A1可促进软骨细胞迁移和细胞周期进程。此外,临床数据显示,COL3A1可以作为原发性SC的诊断标志物(AUC=0.82),并且与中性粒细胞/淋巴细胞比值呈正相关.
结论:这些结果表明SC组织含有丰富的GAG和胶原。COL3A1可以影响软骨细胞的功能,是原发性SC患者的诊断标志物。这些发现为SC的诊断和治疗提供了一种新颖的方法和基本的贡献。
BACKGROUND: Synovial chondromatosis (SC) primarily affects the major joints and is characterized by the formation of benign cartilaginous nodules. In the present study, we evaluated the differences in the histology and gene expression of SC and normal cartilages and further elucidated the function of hub genes in SC.
METHODS: Histological staining and biochemical analysis were performed to measure collagen and glycosaminoglycan (GAG) contents in SC and normal cartilage samples. Then, microarray analysis was performed using knee joint samples (three normal and three SC samples) to identify the differentially expressed genes (DEGs). Subsequently, bioinformatics analysis was performed to identify the hub genes and explore the mechanisms underlying SC. The intersection of the top 10 upregulated DEGs, top 10 downregulated DEGs, and hub genes was validated in SC tissues. Lastly, in vitro experiments and our clinical cohort were used to determine the potential biological functions and diagnostic value, respectively, of the most significant gene.
RESULTS: The GAG and collagen contents were comparable to or higher in SC tissues than in normal tissues. Microarray analysis revealed 143 upregulated and 107 downregulated DEGs in SC. Furthermore, functional enrichment analysis revealed an association between immunity and metabolism-related pathways and SC development. Among 20 hub genes, two intersection genes, namely, collagen type III alpha 1 chain (
COL3A1) and HSPA8, were notably expressed in SC tissues, with
COL3A1 exhibiting a more significant difference in mRNA expression. Furthermore,
COL3A1 can promote chondrocyte migration and cell cycle progression. Additionally, clinical data revealed
COL3A1 can be a diagnostic marker for primary SC (AUC = 0.82) and be a positive correlation with neutrophil-to-lymphocyte ratio.
CONCLUSIONS: These results suggest that SC tissues contained the abundant GAG and collagen.
COL3A1 can affect the function of chondrocytes and be a diagnostic marker of primary SC patients. These findings provide a novel approach and a fundamental contribution for diagnosis and treatment in SC.