Division of Physical Science, Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand.
Center of Excellence for Trace Analysis and Biosensor (TAB-CoE), Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand.
Int J Mol Sci. 2024 Jan 24;25(3):1405. doi: 10.3390/ijms25031405.
Triple-negative breast cancer (TNBC), a heterogeneous and therapeutically challenging subtype, comprises over 50% of patients categorized into basal-like 1 (BL1) and basal-like 2 (BL2) intrinsic molecular subtypes. Despite their shared basal-like classification, BL2 is associated with a poor response to neoadjuvant chemotherapy and reduced relapse-free survival compared to BL1. Here, the study focused on identifying subtype-specific markers for BL2 through transcriptomic analysis of TNBC patients using RNA-seq and clinical integration. Six receptor tyrosine kinase (TK) genes, including , , , , , and , were identified as potential differentiators for BL2. Correlations between TK mRNA expression and TNBC prognosis, particularly , , and , revealed potential synergistic interactions in pathways related to cell survival and proliferation. Our findings also suggest promising dual markers for predicting disease prognosis. Furthermore, RT-qPCR validation demonstrated that identified BL2-specific TKs were expressed at a higher level in BL2 than in BL1 cell lines, providing insights into unique characteristics. This study advances the understanding of TNBC heterogeneity within the basal-like subtypes, which could lead to novel clinical treatment approaches and the development of targeted therapies.
三阴性乳腺癌(TNBC)是一种异质性且治疗具有挑战性的亚型,超过 50%的患者分为基底样 1(BL1)和基底样 2(BL2)内在分子亚型。尽管它们具有共同的基底样分类,但与 BL1 相比,BL2 对新辅助化疗的反应较差,无复发生存率降低。在这里,研究通过使用 RNA-seq 和临床整合对 TNBC 患者进行转录组分析,重点确定 BL2 的亚型特异性标志物。鉴定出 6 个受体酪氨酸激酶(TK)基因,包括、、、、、和,它们可能是 BL2 的潜在区分标志物。TK mRNA 表达与 TNBC 预后之间的相关性,特别是、和,揭示了与细胞存活和增殖相关途径中的潜在协同相互作用。我们的研究结果还表明,有希望的双标志物可用于预测疾病预后。此外,RT-qPCR 验证表明,在 BL2 细胞系中鉴定出的 BL2 特异性 TK 的表达水平高于 BL1 细胞系,这为了解独特特征提供了线索。这项研究深入了解了基底样亚型内的 TNBC 异质性,这可能为新的临床治疗方法和靶向治疗的发展提供依据。