Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China.
J Transl Med. 2023 Jun 23;21(1):409. doi: 10.1186/s12967-023-04204-5.
Intra-tumoral heterogeneity (ITH) is a distinguished hallmark of cancer, and cancer stem cells (CSCs) contribute to this malignant characteristic. Therefore, it is of great significance to investigate and even target the regulatory factors driving intra-tumoral stemness. c-Myc is a vital oncogene frequently overexpressed or amplified in various cancer types, including breast cancer. Our previous study indicated its potential association with breast cancer stem cell (BCSC) biomarkers.
In this research, we performed immunohistochemical (IHC) staining on sixty breast cancer surgical specimens for c-Myc, CD44, CD24, CD133 and ALDH1A1. Then, we analyzed transcriptomic atlas of 1533 patients with breast cancer from public database.
IHC staining indicated the positive correlation between c-Myc and BCSC phenotype. Then, we used bioinformatic analysis to interrogate transcriptomics data of 1533 breast cancer specimens and identified an intriguing link among c-Myc, cancer stemness and copper-induced cell death (also known as "cuproptosis"). We screened out cuproptosis-related characteristics that predicts poor clinical outcomes and found that the pro-tumoral cuproptosis-based features were putatively enriched in MYC-targets and showed a significantly positive correlation with cancer stemness.
In addition to previous reports on its oncogenic roles, c-Myc showed significant correlation to stemness phenotype and copper-induced cell toxicity in breast cancer tissues. Moreover, transcriptomics data demonstrated that pro-tumoral cuproptosis biomarkers had putative positive association with cancer stemness. This research combined clinical samples with large-scale bioinformatic analysis, covered description and deduction, bridged classic oncogenic mechanisms to innovative opportunities, and inspired the development of copper-based nanomaterials in targeting highly heterogeneous tumors.
肿瘤内异质性（ITH）是癌症的一个显著特征，而癌症干细胞（CSC）促成了这种恶性特征。因此，研究甚至靶向驱动肿瘤内干性的调节因子具有重要意义。c-Myc 是一种重要的癌基因，在多种癌症类型中经常过表达或扩增，包括乳腺癌。我们之前的研究表明，它与乳腺癌干细胞（BCSC）标志物有潜在的关联。
在这项研究中，我们对 60 例乳腺癌手术标本进行了 c-Myc、CD44、CD24、CD133 和 ALDH1A1 的免疫组织化学（IHC）染色。然后，我们分析了公共数据库中 1533 例乳腺癌患者的转录组图谱。
IHC 染色表明 c-Myc 与 BCSC 表型之间存在正相关。然后，我们使用生物信息学分析方法对 1533 例乳腺癌标本的转录组数据进行了分析，发现 c-Myc、癌症干性和铜诱导的细胞死亡（也称为“铜死亡”）之间存在有趣的联系。我们筛选出与铜死亡相关的特征，这些特征预测了不良的临床结局，并且发现促进肿瘤的铜死亡特征被推测在 MYC 靶标中富集，并与癌症干性呈显著正相关。
除了之前报道的其致癌作用外，c-Myc 在乳腺癌组织中与干性表型和铜诱导的细胞毒性显著相关。此外，转录组数据表明，促进肿瘤的铜死亡生物标志物与癌症干性具有潜在的正相关关系。这项研究结合了临床样本和大规模的生物信息学分析，涵盖了描述和推理，将经典的致癌机制与创新的机会联系起来，并启发了基于铜的纳米材料在靶向高度异质性肿瘤方面的发展。
