Aberrant miRNAs expressed in HER-2 negative breast cancers patient

Abstract

BackgroundBreast cancer is a highly heterogeneous pathology, exhibiting a number of subtypes commonly associated with a poor outcome. Due to their high stability, microRNAs are often regarded as non-invasive cancer biomarkers, having an expression pattern specific for their ‘cell of origin’.MethodTriple negative breast cancer (TNBC: ER-, PR-, Her-2-) and double positive breast cancer (DPBC: ER+, PR+, Her-2) miRNA expression patterns were obtained by analysis of the TCGA (The Cancer Genome Atlas) data, followed by PCR-array analysis on plasma samples from 20 TNBC patients, 14 DPBC patients and 11 controls.ResultsThree downregulated and nine upregulated miRNAs were obtained from the TNBC analysis. Five overexpressed miRNAs were identified in the DPBC group. Four of the dysregulated miRNAs (miR-10a, miR-125b, miR-210 and miR-489) were common for both groups. The cluster miR-17-92 (miR-17, miR-20a, miR-20b, and miR-93), along with miR-130, miR-22 and miR-29a/c, were found to differentiate between TNBC and DPBC. A panel of five transcripts (miR-10a, miR-125, miR-193b, miR-200b and miR-489) was validated in a new set of plasma samples. The overlapping of TCGA and plasma profiling data revealed miR-200b, miR-200c, miR-210 and miR-29c as common signature. MiR-200b was validated on additional normal and tumor tissue samples. The expression level of this transcript from the TCGA data was correlated with lung and bone metastatic genes.ConclusionThe miR-200b presents a great potential for the future advancements in the diagnostic/prognostic and therapeutic approach of TNBC, along with other coding or non-coding transcripts. However, this needs to be further integrated in a regulatory network that acts in conjunction with other markers that affect the patients’ prognosis or response to therapy.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0920-2) contains supplementary material, which is available to authorized users.

Pathway Analysis of Selected Circulating miRNAs in Plasma of Breast Cancer Patients: A Preliminary Study

“…Thus, miR-130a expression directly influences the TGF-β signalling pathway and is linked to EMT markers [ 47 ]. Plasma expression of miR-130a in BC patients varies according to HER2 status and lymph node positivity [ 48 ] and together with cluster miR-17-92, miR-22 and miR-29a/c can differentiate between TNBC and luminal A [ 49 ]. On the contrary, exosomal miR-130a-3p expression has a suppressive effect on breast cancer stem cell proliferation, invasion and migration via the downregulation of Ras superfamily of small GTPases-RAB5B; decreased miR-130a-3p expression is associated with lymph node metastasis and advanced tumor stage [ 50 ].…”

Cancer-Associated Stemness and Epithelial-to-Mesenchymal Transition Signatures Related to Breast Invasive Carcinoma Prognostic

“…Therefore, patient care management remains an important clinical challenge due to the lack of availability of prognostic markers that could stratify a patient’s risk. In the past few years, there has been an increased interest in verifying the clinical utility of coding and noncoding genes as important biomarkers for prognostic, diagnostic, and therapeutic targets [ 2 , 4 , 5 , 6 , 7 , 8 ].…”

“…CSCs sustain self-renewing tumorigenic cell fractions; moreover, these cells are involved in drug resistance, and they are linked to invasion and distant metastasis [ 14 ]. Compared to non-stem cancer cells, CSC populations possess higher levels of resistance to chemotherapy, radiotherapy, and immunotherapy [ 5 , 14 ].…”

“…In an earlier study, we observed critical transcriptomic alterations in breast cancer tissues [ 5 ]. Among these, miR-200c and the critical regulators of EMT and CSCs are likely to be useful in the diagnostic/prognostic of her2-positive breast cancer [ 5 ].…”

“…In an earlier study, we observed critical transcriptomic alterations in breast cancer tissues [ 5 ]. Among these, miR-200c and the critical regulators of EMT and CSCs are likely to be useful in the diagnostic/prognostic of her2-positive breast cancer [ 5 ]. Therefore, pursuing additional investigations of those common EMT and CSCs signatures will have important clinical benefits in breast cancer management, as these two processes are mediators of resistance to therapy [ 22 ].…”