MicroRNA profile in very young women with breast cancer

Abstract

BackgroundBreast cancer is rarely diagnosed in very young women (35years old or younger), and it often presents with distinct clinical-pathological features related to a more aggressive phenotype and worse prognosis when diagnosed at this early age. A pending question is whether breast cancer in very young women arises from the deregulation of different underlying mechanisms, something that will make this disease an entity differentiated from breast cancer diagnosed in older patients.MethodsWe performed a comprehensive study of miRNA expression using miRNA Affymetrix2.0 array on paraffin-embedded tumour tissue of 42 breast cancer patients 35 years old or younger, 17 patients between 45 and 65 years old and 29 older than 65 years. Data were statistically analyzed by t-test and a hierarchical clustering via average linkage method was conducted. Results were validated by qRT-PCR. Putative targeted pathways were obtained using DIANA miRPath online software.ResultsThe results show a differential and unique miRNA expression profile of 121 miRNAs (p-value <0.05), 96 of those with a FDR-value <0.05. Hierarchical clustering grouped the samples according to their age, but not by subtype nor by tumour characteristics. We were able to validate by qRT-PCR differences in the expression of 6 miRNAs: miR-1228*, miR-3196, miR-1275, miR-92b, miR-139 and miR-1207. Moreover, all of the miRNAs maintained the expression trend. The validated miRNAs pointed out pathways related to cell motility, invasion and proliferation.ConclusionsThe study suggests that breast cancer in very young women appears as a distinct molecular signature. To our knowledge, this is the first time that a validated microRNA profile, distinctive to breast cancer in very young women, has been presented. The miRNA signature may be relevant to open an important field of research in order to elucidate the underlying mechanism in this particular disease, which in a more clinical setting, could potentially help to identify therapeutic targets in this particular set of patients.

Role of cancer stem cells in racial disparity in colorectal cancer

“…It has been reported that miR-1207-5p is upregulated in CRC tissues and a wide variety of cancer tissues and cell lines [30,45,46]. Our observation that forced expression of miR-1207-5p in human colonic epithelial cells, HCoEpiC and CCD841 alters their morphology to a more elongated EMT phenotype-a marker for invasion and metastases and causes an increased expression of a number colon CSC markers which among others include CD44, CD166, and CD133 as well as Slug, Snail, and Vimentin further suggests an involvement of this miR in induction of stemnness in colonic epithelial cells.…”

miR-125a-5p expression is associated with the age of breast cancer patients

“…Previous studies have compared molecular features of BC to age and have shown that BC tumors in young women have distinct gene expression profiles and deregulated signaling pathways (Anders et al, 2008;Pirone et al, 2012;Colak et al, 2013;Peña-Chilet et al, 2014). The up-regulated miR-125a-5p in younger patients indicates that miR-125a-5p may play an important role in BC development in an age-dependent manner, although its effects and possible targets need to be further elucidated.…”

Molecular Biology In Young Women With Breast Cancer: From Tumor Gene Expression To Dna Mutations

“…In tumors, there was an increased methylation of BRCA1, BRCA2, ATM, CHEK2, MLH1, MSH2, and MSH6, while methylation in CDH1 was increased in the blood. PMS2 was hypomethylated, and PALB2 was hypermethylated in most of the tumor samples 40,43,53 . This study yielded interesting insights on specific methylation patterns in the main genes involved in BC carcinogenesis.…”

“…Some experimental data suggest that there is a particular miRNA expression pattern in YWBC [40][41][42] . Peña-Chilet et al 40 studied the miRNA profile of 45 YWBC (defined as ≤35 years) compared to older women and found a unique expression of 96 miRNAs according to age (p < 0.05). The research group validated the expression of 6 miRNAs, finding upregulation of miRNA-1228*, miRNA-3196, miRNA-1275, and miRNA-1207, and downregulation of miRNA-139-5p and miRNA-92b.…”

“…The research group validated the expression of 6 miRNAs, finding upregulation of miRNA-1228*, miRNA-3196, miRNA-1275, and miRNA-1207, and downregulation of miRNA-139-5p and miRNA-92b. These miRNAs are involved in pathways related to cell motility and apoptosis, mitotic and proliferation regulatory mechanisms, and the PI3K and IGFR signaling, all these features associated with higher metastatic capacity 40 .…”