Ayan Durmus, Bozkurt Polat Serife Buket, Ozmen Esma, Gul Mehmet Ali
Faculty of Medicine, Medical Biochemistry, Nigde Omer Halisdemir University, 51100 Nigde, Türkiye.
Faculty of Medicine, Medical Biochemistry, Amasya University, 05200 Amasya, Türkiye.
Int J Mol Sci. 2025 Jun 19;26(12):5906. doi: 10.3390/ijms26125906.
Breast cancer (BC) remains a leading cause of cancer-related mortality in women, with treatment challenges due to the lack of targeted therapies. Extracellular vesicles (EVs) play a crucial role in BC progression by carrying bioactive molecules. This study analyzed EV-associated molecules (ENPEP, TIMP1, CD36, MARCKS, DAB2, CXCL14, miR-181b-5p, miR-222-3p) using bioinformatics tools. We used GEPIA2; Human Protein Atlas (HPA) 24.0; bc-GenExMiner v5.1; UALCAN 2022; Kaplan-Meier plotter 2025; ENCORI database v2.0; Enrichr-KG web tool 2021; Cancer Hallmark Enrichment tool 2025; Tumor, Normal, and Metastatic (TNM) plot database 2025; MicroRNA Target Prediction Database 6.0; TargetScan 8.0; and STRING database 12.0. CD36, DAB2, and CXCL14 were significantly downregulated, while TIMP1 was upregulated in BC tissues ( < 0.05). CD36, CXCL14, and DAB2 were predominantly low in triple-negative and basal-like subtypes, whereas TIMP1 was higher in HER2+, ER+, and PR+ tumors ( < 0.01). These changes correlated with promoter methylation patterns. Higher TIMP1, DAB2, and CXCL14 levels were associated with improved overall survival ( < 0.05). miR-222-3p was downregulated and positively correlated with TIMP1 and DAB2, while miR-181b-5p was upregulated and negatively correlated with CXCL14. TNM analysis confirmed these expression changes. Functional enrichment linked these molecules to key cancer hallmarks, including proliferation and angiogenesis. CD36, DAB2, CXCL14, TIMP1, miR-222-3p, and miR-181b-5p may serve as biomarkers for BC pathogenesis and potential therapeutic targets. Further studies are needed to validate these findings.
乳腺癌（BC）仍然是女性癌症相关死亡的主要原因，由于缺乏靶向治疗，治疗面临挑战。细胞外囊泡（EVs）通过携带生物活性分子在BC进展中发挥关键作用。本研究使用生物信息学工具分析了与EV相关的分子（ENPEP、TIMP1、CD36、MARCKS、DAB2、CXCL14、miR-181b-5p、miR-222-3p）。我们使用了GEPIA2；人类蛋白质图谱（HPA）24.0；bc-GenExMiner v5.1；UALCAN 2022；Kaplan-Meier绘图仪2025；ENCORI数据库v2.0；Enrichr-KG网络工具2021；癌症特征富集工具2025；肿瘤、正常和转移（TNM）绘图数据库2025；MicroRNA靶标预测数据库6.0；TargetScan 8.0；以及STRING数据库12.0。在BC组织中，CD36、DAB2和CXCL14显著下调，而TIMP1上调（<0.05）。CD36、CXCL14和DAB2在三阴性和基底样亚型中主要较低，而TIMP1在HER2+、ER+和PR+肿瘤中较高（<0.01）。这些变化与启动子甲基化模式相关。较高的TIMP1、DAB2和CXCL14水平与总体生存率提高相关（<0.05）。miR-222-3p下调并与TIMP1和DAB2呈正相关，而miR-181b-5p上调并与CXCL14呈负相关。TNM分析证实了这些表达变化。功能富集将这些分子与关键的癌症特征联系起来，包括增殖和血管生成。CD36、DAB2、CXCL14、TIMP1、miR-222-3p和miR-181b-5p可能作为BC发病机制的生物标志物和潜在的治疗靶点。需要进一步的研究来验证这些发现。
