Background/Objectives: Breast cancer remains the leading malignancy affecting women worldwide, with significant mortality rates. This study aimed to evaluate the prognostic significance of FOXM1 expression specifically in hormone receptor-positive, HER2-negative (HR+HER2-) breast cancer patients with high KPNA2 expression, and to identify potential FOXM1-targeted therapeutic strategies for this patient subgroup.Methods: We analyzed RNA sequencing and microarray data from three independent cohorts: Mackay Memorial Hospital patient samples, The Cancer Genome Atlas, and Gene Expression Omnibus databases. The expression levels of KPNA2, FOXM1, CCNB1, and CCNB2 were evaluated, with particular emphasis on stratifying patients based on KPNA2 expression levels. Their associations with clinical outcomes were assessed using Gene Set Enrichment Analysis and survival analyses.Results: While KPNA2 expression showed strong positive correlations with FOXM1, CCNB1, and CCNB2 across all datasets, our analysis revealed a distinct prognostic pattern in HR+HER2- breast cancer patients with high KPNA2 expressions. In this specific subgroup, low FOXM1 expression emerged as a favorable prognostic indicator, despite the generally poor prognosis associated with high KPNA2 levels. Gene Set Enrichment Analysis demonstrated significant enrichment of the G2/M checkpoint pathway in high KPNA2-expressing patients, suggesting potential therapeutic vulnerability to FOXM1 inhibition in this subgroup.Conclusions: This study establishes FOXM1 expression as a critical prognostic marker, specifically in KPNA2-high HR+HER2- breast cancer patients, where low FOXM1 levels correlate with improved survival outcomes. These findings suggest that FOXM1 inhibition could be particularly effective in patients with high KPNA2 expression, offering a novel therapeutic strategy for this specific molecular subtype. Several FOXM1 inhibitors, including thiostrepton and FDI-6, warrant investigation as potential targeted treatments for KPNA2-high HR+HER2- breast cancer patients.
**背景/目的：** 乳腺癌仍是全球范围内影响女性健康的主要恶性肿瘤，死亡率居高不下。本研究旨在评估FOXM1表达在KPNA2高表达的激素受体阳性、HER2阴性（HR+HER2-）乳腺癌患者中的预后意义，并为此患者亚群探寻潜在的FOXM1靶向治疗策略。 **方法：** 我们分析了来自三个独立队列的RNA测序和微阵列数据：马偕纪念医院患者样本、癌症基因组图谱以及基因表达综合数据库。评估了KPNA2、FOXM1、CCNB1和CCNB2的表达水平，并特别强调根据KPNA2表达水平对患者进行分层。使用基因集富集分析和生存分析评估了它们与临床结局的关联。 **结果：** 尽管在所有数据集中，KPNA2表达均与FOXM1、CCNB1和CCNB2呈强正相关，但我们的分析揭示了在KPNA2高表达的HR+HER2-乳腺癌患者中存在独特的预后模式。在这一特定亚组中，尽管高KPNA2水平通常与不良预后相关，但低FOXM1表达却成为一个有利的预后指标。基因集富集分析表明，在KPNA2高表达患者中，G2/M检查点通路显著富集，提示该亚组可能对FOXM1抑制存在潜在的治疗脆弱性。 **结论：** 本研究确立了FOXM1表达作为一个关键的预后标志物，特别是在KPNA2高表达的HR+HER2-乳腺癌患者中，低FOXM1水平与改善的生存结局相关。这些发现表明，FOXM1抑制可能对KPNA2高表达患者特别有效，为此特定分子亚型提供了一种新的治疗策略。包括硫链丝菌素和FDI-6在内的几种FOXM1抑制剂，值得作为KPNA2高表达HR+HER2-乳腺癌患者的潜在靶向治疗方案进行深入研究。
肿瘤(癌症)患者之家