Subtype‐specific micro‐RNA expression signatures in breast cancer progression

Abstract

Robust markers of invasiveness may help reduce the overtreatment of in situ carcinomas. Breast cancer is a heterogeneous disease and biological mechanisms for carcinogenesis vary between subtypes. Stratification by subtype is therefore necessary to identify relevant and robust signatures of invasive disease. We have identified microRNA (miRNA) alterations during breast cancer progression in two separate datasets and used stratification and external validation to strengthen the findings. We analyzed two separate datasets (METABRIC and AHUS) consisting of a total of 186 normal breast tissue samples, 18 ductal carcinoma in situ (DCIS) and 1,338 invasive breast carcinomas. Validation in a separate dataset and stratification by molecular subtypes based on immunohistochemistry, PAM50 and integrated cluster classifications were performed. We propose subtype-specific miRNA signatures of invasive carcinoma and a validated signature of DCIS. miRNAs included in the invasive signatures include downregulation of miR-139-5p in aggressive subtypes and upregulation of miR-29c-5p expression in the luminal subtypes. No miRNAs were differentially expressed in the transition from DCIS to invasive carcinomas on the whole, indicating the need for subtype stratification. A total of 27 miRNAs were included in our proposed DCIS signature. Significant Key words: miRNA, breast cancer invasion, biomarker, subtype, DCIS Abbreviations: DCIS: ductal carcinoma in situ; ER: estrogen receptor; FDR: false discovery rate; HER2: human epidermal growth factor 2; IC: integrated cluster; miRNA: microRNA; PAM50: prediction analysis of microarrays 50; PGR: progesterone receptor Additional Supporting Information may be found in the online version of this article.

MicroRNA expression profiles discriminate childhood T‐ from B‐acute lymphoblastic leukemia

“…A-C, E, and F, Mann-Whitney U test; D, Kruskal-Wallis test. ETP, early T-cell precursor leukemia; BM, bone marrow; PB, peripheral blood been modulated in solid tumors, like gallbladder carcinoma 51 and breast cancer, 52 and its downregulation is associated with metastasis and cell proliferation. 51 Besides genetic abnormalities observed in Band T-cell leukemias, distinct posttranscriptional regulation of leukemogenic genes may be present yielding different molecular mechanisms of growth and malignant transformation.…”

Dicer1 dysfunction promotes stemness and aggression in endometrial carcinoma

“…The let-7 family comprises known tumor suppressors and participates in the regulation of stemness in breast cancer cells. 14,18 In addition, previous studies have shown that, as a key enzyme in the biogenesis of miRNA, dysfunction of Dicer1 leads to low expression of the let-7 family. 19 In this regard, we next explored whether Dicer1 affects regulation of the let-7 family in EC.…”

Crosstalk between microRNA expression and DNA methylation drive the hormone-dependent phenotype of breast cancer

“…miRNAs play crucial roles in the regulation of cancer-associated processes such as proliferation, apoptosis, and differentiation, and are known to elicit context-and cell-type specific expression [8,9]. In breast cancer, expression of miRNAs has been associated with clinical and molecular subtypes [10][11][12], progression [13][14][15], prognosis [16,17] and expression of oncogenes [18]. Importantly, miRNAs have been shown to regulate the expression of epigenetic regulators such as DNMTs and TETs [19,20].…”