School of Applied Sciences and Technology, Gujarat Technological University, Ahmedabad, Gujarat, 382424, India.
Department of Validation Indic Knowledge Through Advanced Research, Gujarat University, Ahmedabad, Gujarat, 380009, India.
Mol Genet Genomics. 2024 Oct 5;299(1):93. doi: 10.1007/s00438-024-02184-9.
Visceral obesity (VO), characterized by excess fat around internal organs, is a recognized risk factor for gynecological tumors, including benign uterine leiomyoma (ULM) and malignant uterine leiomyosarcoma (ULS). Despite this association, the shared molecular mechanisms remain underexplored. This study utilizes an integrated bioinformatics approach to elucidate common molecular pathways and identify potential therapeutic targets linking VO, ULM, and ULS. We analyzed gene expression datasets from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) in each condition. We found 101, 145, and 18 DEGs in VO, ULM, and ULS, respectively, with 37 genes overlapping across all three conditions. Functional enrichment analysis revealed that these overlapping DEGs were significantly enriched in pathways related to cell proliferation, immune response, and transcriptional regulation, suggesting shared biological processes. Protein-protein interaction network analysis identified 14 hub genes, of which TOP2A, APOE, and TYMS showed significant differential expression across all three conditions. Drug-gene interaction analysis identified 26 FDA-approved drugs targeting these hub genes, highlighting potential therapeutic opportunities. In conclusion, this study uncovers shared molecular pathways and actionable drug targets across VO, ULM, and ULS. These findings deepen our understanding of disease etiology and offer promising avenues for drug repurposing. Experimental validation is needed to translate these insights into clinical applications and innovative treatments.
内脏肥胖症(VO),其特征是内脏器官周围脂肪过多,是妇科肿瘤的一个公认的危险因素,包括良性子宫平滑肌瘤(ULM)和恶性子宫平滑肌肉瘤(ULS)。尽管存在这种关联,但共同的分子机制仍未得到充分探索。本研究采用综合生物信息学方法阐明 VO、ULM 和 ULS 之间的共同分子途径,并确定潜在的治疗靶点。我们分析了基因表达综合数据库(GEO)中的基因表达数据集,以确定每种情况下的差异表达基因(DEG)。我们在 VO、ULM 和 ULS 中分别发现了 101、145 和 18 个 DEG,其中 37 个基因在所有三种情况下都重叠。功能富集分析表明,这些重叠的 DEG 在与细胞增殖、免疫反应和转录调节相关的途径中显著富集,表明存在共同的生物学过程。蛋白质-蛋白质相互作用网络分析确定了 14 个枢纽基因,其中 TOP2A、APOE 和 TYMS 在所有三种情况下的表达均存在显著差异。药物-基因相互作用分析确定了 26 种针对这些枢纽基因的 FDA 批准药物,突出了潜在的治疗机会。总之,本研究揭示了 VO、ULM 和 ULS 之间共同的分子途径和可操作的药物靶点。这些发现加深了我们对疾病病因的理解,并为药物再利用提供了有前途的途径。需要进行实验验证,将这些见解转化为临床应用和创新治疗。