MicroRNA signatures in hereditary breast cancer

Abstract

This study aims to identify signatures of miR associated with hereditary, BRCA1 or BRCA2 mutation positive breast cancer (BC), and non-hereditary BC, either sporadic (SBC) or non-informative (BRCAX). Moreover, we search for signatures associated with tumor stage, immunohistochemistry and tumor molecular profile. Twenty formalin fixed paraffin embedded (FFPE) BCs, BRCA1, BRCA2, BRCAX and SBC, five per group were studied. Affymetrix platform miRNA v.3.0 was used to perform miR expression analysis. ER, PR, HER2 and Ki67 protein expression was analyzed by immunohistochemistry. BRCA1, BRCA2 and RASSF1 methylation analysis, AURKA copy number variations, and BRCA1 and BRCA2 deletions, were studied by MLPA. We validated eight of the miR selected by the arrays in 77 BCs by qRT-PCR. The miR profiles associated with tumor features were studied applying the Sparse Partial Least Squares Discriminant Analysis. MiR discrimination capability to distinguish hereditary and non-hereditary BC was analyzed by the discriminant function. With 15 out of 1,733 hsa-miRs, it was possible to differentiate the four groups. BRCA1, BRCA2 and SBC were associated with clusters of hyper-expressed miRs, and BRCAX with hypo-expressed miRs. Hsa-miR-4417 and hsa-miR-423-3p expressions (included among the eight validated miRs) differentiated 70.1 % of hereditary and non-hereditary BCs. We found miR profiles associated with tumor features like node involvement, histological grade, ER, PR and HER2 expression. Regarding molecular parameters, we only found a weak association of miRs in BC harboring losses in AURKA. We conclude that array miR expression profiles can differentiate the four study groups using FFPE BC. However, miRs expression estimated by qRT-PCR differentiates only hereditary and non-inherited BCs. The miR expression array is a simple and rapid approach that could be useful to facilitate the identification of those SBC carrying genetic or epigenetic changes in BRCA genes responsible of BRCA-like phenotype. These patients could benefit from the treatment with PARP inhibitors.

Altered microRNA expression profile in hepatitis B virus-related hepatocellular carcinoma

“…2). These miRNAs have previously been shown to be linked to the pathogenesis of HCC and other types of cancer (Chiu et al, 2014, Karakatsanis et al, 2013, Murria Estal et al, 2013, Wang et al, 2012, Wong et al, 2011. Among the six miRNAs examined, the expression levels of four matched the microarray results (p< 0.05), warranting further study using a larger cohort of HCC clinical…”

MicroRNAs Discriminate Familial from Sporadic Non-BRCA1/2 Breast Carcinoma Arising in Patients ≤35 Years

“…In addition, a recent study highlighted that non-BRCA1/2 hereditary BC may be sub-classified using specific miR signatures [27]. Recently, Estal and coworkers suggested that the miR expression profile may facilitate the identification of sporadic BC carrying genetic/epigenetic changes in BRCA genes [28]. Our specific aims in the current study were (A) to identify a miR expression signature that could discriminate between familial and sporadic BC in young patients (≤35 years) who are non-carriers of BRCA1/2 mutations; and (B) to identify candidate target-genes related with the differentially expressed miRs.…”

miR-4417 Targets Tripartite Motif-Containing 35 (TRIM35) and Regulates Pyruvate Kinase Muscle 2 (PKM2) Phosphorylation to Promote Proliferation and Suppress Apoptosis in Hepatocellular Carcinoma Cells

“…miRNAs can function as novel tumor suppressors or oncogenes in cancer cells according to their targets. Recently, high-throughput array analyses have clearly demonstrated that miR-4417 is upregulated in many human cancers, such as breast cancer, prostate cancer, and gastrointestinal cancer [13–16]. Keon Uk Park et al reported that miR-4417 was upregulated in HCC tissues compared with non-cancerous liver tissue samples by using a microarray-based genome-wide miRNA analysis [11].…”