Molecular Oncology Laboratory, Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu, 620 024, India.
Med Oncol. 2024 Aug 8;41(9):220. doi: 10.1007/s12032-024-02468-5.
Breast cancer (BC) is the leading commonly diagnosed cancer in the world, with complex mechanisms underlying its development. There is an urgent need to enlighten key genes as potential therapeutic targets crucial to advancing BC treatment. This study sought to investigate the influence of doxorubicin (DOX) on identified key genes consistent across numerous BC datasets obtained through bioinformatic analysis. To date, a meta-analysis of publicly available coding datasets for expression profiling by array from the Gene Expression Omnibus (GEO) has been carried out. Differentially Expressed Genes (DEGs) identified using GEO2R revealed a total of 23 common DEGs, including nine upregulated genes and 14 downregulated genes among the datasets of three platforms (GPL570, GPL6244, and GPL17586), and the commonly upregulated DEGs, showed significant enrichment in the cell cycle in KEGG analysis. The top nine genes, NUSAP1, CENPF, TPX2, PRC1, ANLN, BUB1B, AURKA, CCNB2, and CDK-1, with higher degree values and MCODE scores in the cytoscape program, were regarded as hub genes. The hub genes were activated in disease states commonly across all the subclasses of BC and correlated with the unfavorable overall survival of BC patients, as verified by the GEPIA and UALCAN databases. qRT-PCR confirmed that DOX treatment resulted in reduced expression of these genes in BC cell lines, which reinforces the evidence that DOX remains an effective drug for BC and suggests that developing modified formulations of doxorubicin to reduce toxicity and resistance, could enhance its efficacy as an effective therapeutic option for BC.
乳腺癌（BC）是世界上最常见的癌症，其发展机制复杂。急需阐明关键基因作为潜在的治疗靶点，这对于推进 BC 治疗至关重要。本研究旨在探讨阿霉素（DOX）对通过生物信息学分析从基因表达综合数据库（GEO）获得的多个 BC 数据集一致确定的关键基因的影响。迄今为止，已经对 GEO 中公开提供的用于表达谱分析的编码数据集进行了元分析。GEO2R 识别的差异表达基因（DEGs）总共显示了 23 个共同的 DEGs，包括三个平台（GPL570、GPL6244 和 GPL17586）数据集的 9 个上调基因和 14 个下调基因，共同上调的 DEGs 在 KEGG 分析中显著富集在细胞周期中。前 9 个基因，包括 NUSAP1、CENPF、TPX2、PRC1、ANLN、BUB1B、AURKA、CCNB2 和 CDK-1，在 Cytoscape 程序中的度值和 MCODE 评分较高，被认为是枢纽基因。这些枢纽基因在所有 BC 亚类中常见的疾病状态中被激活，并与 BC 患者的不利总生存率相关，这通过 GEPIA 和 UALCAN 数据库得到了验证。qRT-PCR 证实 DOX 治疗导致 BC 细胞系中这些基因的表达减少，这进一步证明 DOX 仍然是治疗 BC 的有效药物，并表明开发改良的阿霉素制剂以降低毒性和耐药性，可以提高其作为 BC 有效治疗选择的疗效。
