Background: HER2-positive breast cancer is an aggressive subtype where innate/acquired resistance to targeted drugs remains a challenge. This study aims to uncover the underlying mechanisms of HER2 drug resistance through miRNA analysis and target identification. Methods: MiRNA datasets were systematically retrieved from the GEO database, and differential expression analysis was conducted for both miRNA and mRNA datasets. Functional analyses were also conducted to validate the identified miRNAs and assess their clinical relevance. Results: We identified 113 differentially expressed miRNAs (DEMs) and 923 target genes. Validation was performed using external mRNA datasets, and intersection with significant genes identified 110 overlapping genes associated with HER2 drug resistance. Further analyses included functional enrichment, construction of a protein–protein interaction (PPI) network, identification of key hub genes such as BCL2, FOS, and CXCR4, and assessment of clinical relevance through survival analysis and immunohistochemistry (IHC) assessments. Conclusions: This integrative approach unveils a complex landscape of HER2 drug resistance in breast cancer, identifying crucial miRNAs, target genes, and significant pathways. The findings offer novel insights into the mechanisms governing drug resistance and highlight the potential for enhancing therapeutic strategies. Future studies are necessary for experimental validation to further explore the complex mechanisms involved.
背景：HER2阳性乳腺癌是一种侵袭性亚型，其固有的/获得性的靶向药物耐药性仍是一个挑战。本研究旨在通过miRNA分析和靶点识别，揭示HER2耐药性的潜在机制。方法：从GEO数据库中系统检索miRNA数据集，并对miRNA和mRNA数据集进行差异表达分析。同时进行功能分析以验证所识别的miRNA并评估其临床相关性。结果：我们鉴定出113个差异表达miRNA（DEMs）和923个靶基因。利用外部mRNA数据集进行验证，并通过与显著基因的交集分析，确定了110个与HER2耐药相关的重叠基因。进一步分析包括功能富集分析、构建蛋白质-蛋白质相互作用（PPI）网络、识别关键枢纽基因（如BCL2、FOS和CXCR4），以及通过生存分析和免疫组织化学（IHC）评估临床相关性。结论：这种整合方法揭示了乳腺癌中HER2耐药性的复杂图景，识别了关键的miRNA、靶基因和重要通路。研究结果为理解耐药机制提供了新的见解，并强调了增强治疗策略的潜力。未来需要进行实验验证以进一步探索其中涉及的复杂机制。
肿瘤(癌症)患者之家