Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 97, 95123 Catania, Italy.
Medical Oncology Unit B, Department of Radiology, Oncology and Pathology, Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy.
Cells. 2024 Aug 3;13(15):1299. doi: 10.3390/cells13151299.
Triple-negative breast cancer (TNBC) represents an aggressive subtype of breast cancer, with a bad prognosis and lack of targeted therapeutic options. Characterized by the absence of estrogen receptors, progesterone receptors, and HER2 expression, TNBC is often associated with a significantly lower survival rate compared to other breast cancer subtypes. Our study aimed to explore the prognostic significance of 83 immune-related genes, by using transcriptomic data from the TCGA database. Our analysis identified the Poliovirus Receptor-Like 3 protein (PVRL3) as a critical negative prognostic marker in TNBC patients. Furthermore, we found that the Enhancer of Zeste Homolog 2 (EZH2), a well-known epigenetic regulator, plays a pivotal role in modulating PVRL3 levels in TNBC cancer cell lines expressing EZH2 along with high levels of PVRL3. The elucidation of the EZH2-PVRL3 regulatory axis provides valuable insights into the molecular mechanisms underlying TNBC aggressiveness and opens up potential pathways for personalized therapeutic intervention.
三阴性乳腺癌（TNBC）是一种侵袭性乳腺癌亚型，预后较差，缺乏靶向治疗选择。TNBC 的特征是缺乏雌激素受体、孕激素受体和 HER2 表达，与其他乳腺癌亚型相比，其生存率通常明显较低。我们的研究旨在通过使用 TCGA 数据库中的转录组数据，探讨 83 个免疫相关基因的预后意义。我们的分析确定了脊髓灰质炎病毒受体样 3 蛋白（PVRL3）是 TNBC 患者的关键负预后标志物。此外，我们发现 Enhancer of Zeste Homolog 2（EZH2），一种众所周知的表观遗传调节剂，在调节 TNBC 癌细胞系中 PVRL3 水平方面发挥着关键作用，这些细胞系表达 EZH2 并伴有高水平的 PVRL3。阐明 EZH2-PVRL3 调节轴为 TNBC 侵袭性的分子机制提供了有价值的见解，并为个性化治疗干预开辟了潜在途径。
