Angius Andrea, Cossu-Rocca Paolo, Arru Caterina, Muroni Maria Rosaria, Rallo Vincenzo, Carru Ciriaco, Uva Paolo, Pira Giovanna, Orrù Sandra, De Miglio Maria Rosaria
Institute of Genetic and Biomedical Research (IRGB), CNR, Cittadella Universitaria di Cagliari, 09042 Monserrato, Italy.
Department of Medical, Surgical and Experimental Sciences, University of Sassari, Via P. Manzella, 4, 07100 Sassari, Italy.
Cancers (Basel). 2020 Nov 7;12(11):3298. doi: 10.3390/cancers12113298.
Development of new research, classification, and therapeutic options are urgently required due to the fact that TNBC is a heterogeneous malignancy. The expression of high molecular weight cytokeratins identifies a biologically and clinically distinct subgroup of TNBCs with a basal-like phenotype, representing about 75% of TNBCs, while the remaining 25% includes all other intrinsic subtypes. The triple negative phenotype in basal-like breast cancer (BLBC) makes it unresponsive to endocrine therapy, i.e., tamoxifen, aromatase inhibitors, and/or anti-HER2-targeted therapies; for this reason, only chemotherapy can be considered an approach available for systemic treatment even if it shows poor prognosis. Therefore, treatment for these subgroups of patients is a strong challenge for oncologists due to disease heterogeneity and the absence of unambiguous molecular targets. Dysregulation of the cellular miRNAome has been related to huge cellular process deregulations underlying human malignancy. Consequently, epigenetics is a field of great promise in cancer research. Increasing evidence suggests that specific miRNA clusters/signatures might be of clinical utility in TNBCs with basal-like phenotype. The epigenetic mechanisms behind tumorigenesis enable progress in the treatment, diagnosis, and prevention of cancer. This review intends to summarize the epigenetic findings related to miRNAome in TNBCs with basal-like phenotype.
由于三阴性乳腺癌（TNBC）是一种异质性恶性肿瘤，因此迫切需要开展新的研究、分类和治疗方案。高分子量细胞角蛋白的表达确定了TNBC中具有基底样表型的一个生物学和临床特征明显的亚组，约占TNBC的75%，而其余25%包括所有其他内在亚型。基底样乳腺癌（BLBC）中的三阴性表型使其对内分泌治疗（即他莫昔芬、芳香化酶抑制剂和/或抗HER2靶向治疗）无反应；因此，即使化疗预后不佳，也只能将其视为可用于全身治疗的一种方法。因此，由于疾病的异质性和缺乏明确的分子靶点，对这些患者亚组的治疗对肿瘤学家来说是一个巨大的挑战。细胞miRNA组的失调与人类恶性肿瘤背后的巨大细胞过程失调有关。因此，表观遗传学是癌症研究中一个极具前景的领域。越来越多的证据表明，特定的miRNA簇/特征可能在具有基底样表型的TNBC中具有临床应用价值。肿瘤发生背后的表观遗传机制推动了癌症治疗、诊断和预防的进展。本综述旨在总结与具有基底样表型的TNBC中miRNA组相关的表观遗传学研究结果。
