Malighetti Federica, Villa Matteo, Villa Alberto Maria, Pelucchi Sara, Aroldi Andrea, Cortinovis Diego Luigi, Canova Stefania, Capici Serena, Cazzaniga Marina Elena, Mologni Luca, Ramazzotti Daniele, Cordani Nicoletta
Department of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy.
Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy.
Int J Mol Sci. 2025 Feb 24;26(5):1943. doi: 10.3390/ijms26051943.
Breast cancer (BC) is a highly heterogeneous disease with diverse molecular subtypes, which complicates prognosis and treatment. In this study, we performed a multi-omics clustering analysis using the Cancer Integration via MultIkernel LeaRning (CIMLR) method on a large BC dataset from The Cancer Genome Atlas (TCGA) to identify key prognostic biomarkers. We identified three genes-, , and -that were significantly associated with poor prognosis in both the TCGA dataset and an additional dataset comprising 146 metastatic BC patients. Patients' stratification based on the expression of these three genes revealed distinct subtypes with markedly different overall survival (OS) outcomes. Further validation using almost 2000 BC patients' data from the METABRIC dataset and RNA sequencing data from therapy-resistant cell lines confirmed the upregulation of and , respectively, in patients with worse prognosis and in resistant cells, also suggesting their potential role in drug resistance. Our findings highlight and as potential biomarkers for identifying high-risk BC patients and informing targeted treatment strategies. This study provides valuable insights into the multi-omics landscape of BC and underscores the importance of personalized therapeutic approaches based on molecular profiles.
乳腺癌(BC)是一种高度异质性疾病,具有多种分子亚型,这使得预后和治疗变得复杂。在本研究中,我们使用多内核学习癌症整合(CIMLR)方法对来自癌症基因组图谱(TCGA)的大型BC数据集进行了多组学聚类分析,以确定关键的预后生物标志物。我们鉴定出三个基因——[具体基因1]、[具体基因2]和[具体基因3]——它们在TCGA数据集以及另一个包含146例转移性BC患者的数据集里均与不良预后显著相关。基于这三个基因的表达对患者进行分层,发现了具有明显不同总生存期(OS)结果的不同亚型。使用来自METABRIC数据集的近2000例BC患者数据以及来自耐药细胞系的RNA测序数据进行进一步验证,证实了[具体基因1]和[具体基因2]分别在预后较差的患者和耐药细胞中上调,这也表明它们在耐药性中可能发挥的作用。我们的研究结果突出了[具体基因1]和[具体基因2]作为识别高危BC患者和指导靶向治疗策略的潜在生物标志物。本研究为BC的多组学格局提供了有价值的见解,并强调了基于分子特征的个性化治疗方法的重要性。