Basal-like breast cancer: molecular profiles, clinical features and survival outcomes

Abstract

BackgroundBasal-like constitutes an important molecular subtype of breast cancer characterised by an aggressive behaviour and a limited therapy response. The outcome of patients within this subtype is, however, divergent. Some individuals show an increased risk of dying in the first five years, and others a long-term survival of over ten years after the diagnosis. In this study, we aim at identifying markers associated with basal-like patients’ survival and characterising subgroups with distinct disease outcome.MethodsWe explored the genomic and transcriptomic profiles of 351 basal-like samples from the METABRIC and ROCK data sets. Two selection methods, labelled Differential and Survival filters, were employed to determine genes/probes that are differentially expressed in tumour and control samples, and are associated with overall survival. These probes were further used to define molecular subgroups, which vary at the microRNA level and in DNA copy number.ResultsWe identified the expression signature of 80 probes that distinguishes between two basal-like subgroups with distinct clinical features and survival outcomes. Genes included in this list have been mainly linked to cancer immune response, epithelial-mesenchymal transition and cell cycle. In particular, high levels of CXCR6, HCST, C3AR1 and FPR3 were found in Basal I; whereas HJURP, RRP12 and DNMT3B appeared over-expressed in Basal II. These genes exhibited the highest betweenness centrality and node degree values and play a key role in the basal-like breast cancer differentiation. Further molecular analysis revealed 17 miRNAs correlated to the subgroups, including hsa-miR-342-5p, -150, -155, -200c and -17. Additionally, increased percentages of gains/amplifications were detected on chromosomes 1q, 3q, 8q, 10p and 17q, and losses/deletions on 4q, 5q, 8p and X, associated with reduced survival.ConclusionsThe proposed signature supports the existence of at least two subgroups of basal-like breast cancers with distinct disease outcome. The identification of patients at a low risk may impact the clinical decisions-making by reducing the prescription of high-dose chemotherapy and, consequently, avoiding adverse effects. The recognition of other aggressive features within this subtype may be also critical for improving individual care and for delineating more effective therapies for patients at high risk.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-017-0250-9) contains supplementary material, which is available to authorized users.

Identification of miRNAs Enriched in Extracellular Vesicles Derived from Serum Samples of Breast Cancer Patients

“…The higher expression level of miR-150-5p has been described in BC subtypes, mostly in TNBC [29,49,50], and also in basal I [51] subtypes. It has been described as a good prognostic biomarker for patients with HER2-positive BC [52,53].…”

Using next‐generation sequencing to redefineBRCAnessin triple‐negative breast cancer

“…CRKL , an oncogene located in 22q11.1 that mediates cellular proliferation and metastasis, was amplified in both BRCA ‐mutated (N = 5, 38.5%) and non‐ BRCA HR gene‐mutated (N = 4, 28.6%) tumors ( P = .042, Figure C). The gain of 3q and 10p and loss of Xp, which are significantly associated with BRCA and non‐ BRCA HR gene mutations, were related to carcinogenesis and reduced survival of patients …”

N-glycosylated SGK196 suppresses the metastasis of basal-like breast cancer cells

“…Transcriptomic analyses of human breast tumors have led to classification of four major intrinsic molecular subtypes that include luminal A, luminal B, human epidermal growth factor receptor 2-enriched (HER2 + ) and basal-like breast cancer (BLBC) 5 . BC's molecular categorization is strongly associated with patients' survival outcomes, among which BLBC has the worst prognosis 6 . BLBC consists of about 10-15% of all breast cancer types, characterized by high proliferation and invasion, high expression of basal cytokeratins (CKs) and low expression of the estrogen receptor (ER), progesterone receptor (PR) and HER2 [ref.…”