CEINGE-Biotecnologie Avanzate s.c.ar.l, Naples 80145, Italy; Team "Metabolism, Cancer & Immunity", Centre de Recherche des Cordeliers, INSERM UMRS1138, Sorbonne Université, Université de Paris, Paris 75006, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif 94805, France.
CEINGE-Biotecnologie Avanzate s.c.ar.l, Naples 80145, Italy.
Pharmacol Res. 2020 Nov;161:105249. doi: 10.1016/j.phrs.2020.105249. Epub 2020 Oct 14.
The molecular complexity of human breast cancer (BC) renders the clinical management of the disease challenging. Long non-coding RNAs (lncRNAs) are promising biomarkers for BC patient stratification, early detection, and disease monitoring. Here, we identified the involvement of the long intergenic non-coding RNA 01087 (LINC01087) in breast oncogenesis. LINC01087 appeared significantly downregulated in triple-negative BCs (TNBCs) and upregulated in the luminal BC subtypes in comparison to mammary samples from cancer-free women and matched normal cancer pairs. Interestingly, deregulation of LINC01087 allowed to accurately distinguish between luminal and TNBC specimens, independently of the clinicopathological parameters, and of the histological and TP53 or BRCA1/2 mutational status. Moreover, increased expression of LINC01087 predicted a better prognosis in luminal BCs, while TNBC tumors that harbored lower levels of LINC01087 were associated with reduced relapse-free survival. Furthermore, bioinformatics analyses were performed on TNBC and luminal BC samples and suggested that the putative tumor suppressor activity of LINC01087 may rely on interferences with pathways involved in cell survival, proliferation, adhesion, invasion, inflammation and drug sensitivity. Altogether, these data suggest that the assessment of LINC01087 deregulation could represent a novel, specific and promising biomarker not only for the diagnosis and prognosis of luminal BC subtypes and TNBCs, but also as a predictive biomarker of pharmacological interventions.
人类乳腺癌(BC)的分子复杂性使得该疾病的临床管理具有挑战性。长非编码 RNA(lncRNA)是 BC 患者分层、早期检测和疾病监测的有前途的生物标志物。在这里,我们发现长基因间非编码 RNA 01087(LINC01087)参与了乳腺癌的发生。与无癌女性和匹配的正常癌对的乳腺样本相比,LINC01087 在三阴性 BC(TNBC)中明显下调,在腔 BC 亚型中上调。有趣的是,LINC01087 的失调能够准确地区分腔型和 TNBC 标本,独立于临床病理参数以及组织学和 TP53 或 BRCA1/2 突变状态。此外,LINC01087 的高表达预测了腔型 BC 的预后更好,而携带较低 LINC01087 水平的 TNBC 肿瘤与降低的无复发生存率相关。此外,对 TNBC 和腔型 BC 样本进行了生物信息学分析,表明 LINC01087 的潜在肿瘤抑制活性可能依赖于对涉及细胞存活、增殖、粘附、侵袭、炎症和药物敏感性的途径的干扰。总之,这些数据表明,评估 LINC01087 的失调可能不仅是腔型 BC 亚型和 TNBC 的诊断和预后的新的、特异的和有前途的生物标志物,而且是药物干预的预测生物标志物。