MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype

By C. Blenkiron, Leonard D. Goldstein, N. Thorne, I. Spiteri, S. Chin, M. Dunning, Nuno L. Barbosa-Morais, Andrew E. Teschendorff, A. Green, Ian O. Ellis and 3 more. Genome Biology, 2007

1,015 citations recorded by the source corpus.

BackgroundMicroRNAs (miRNAs), a class of short non-coding RNAs found in many plants and animals, often act post-transcriptionally to inhibit gene expression.ResultsHere we report the analysis of miRNA expression in 93 primary human breast tumors, using a bead-based flow cytometric miRNA expression profiling method. Of 309 human miRNAs assayed, we identify 133 miRNAs expressed in human breast and breast tumors. We used mRNA expression profiling to classify the breast tumors as luminal A, luminal B, basal-like, HER2+ and normal-like. A number of miRNAs are differentially expressed between these molecular tumor subtypes and individual miRNAs are associated with clinicopathological factors. Furthermore, we find that miRNAs could classify basal versus luminal tumor subtypes in an independent data set. In some cases, changes in miRNA expression correlate with genomic loss or gain; in others, changes in miRNA expression are likely due to changes in primary transcription and or miRNA biogenesis. Finally, the expression of DICER1 and AGO2 is correlated with tumor subtype and may explain some of the changes in miRNA expression observed.ConclusionThis study represents the first integrated analysis of miRNA expression, mRNA expression and genomic changes in human breast cancer and may serve as a basis for functional studies of the role of miRNAs in the etiology of breast cancer. Furthermore, we demonstrate that bead-based flow cytometric miRNA expression profiling might be a suitable platform to classify breast cancer into prognostic molecular subtypes.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a77b061868c50a3076b504728543902b91ba9e57

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Citations in the corpus

A Pleiotropically Acting microRNA, miR-31, Inhibits Breast Cancer Metastasis (2009, neutral): “Expression profiling of clinical breast tumors revealed reduced miR31 in luminal B (relative to luminal A), basal-like, and HER2+ tumors (Mattie et al., 2006; Blenkiron et al., 2007)—patterns of reduction that correlate with aggressive disease (Sørlie et al., 2001).”
MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review (2012, neutral): “…unique gene networks involved (O’Day & Lal, 2010). miRNAs, for example, are differentially expressed between basal and luminal breast cancer subtypes (Blenkiron et al, 2007; Sempere et al, 2007), and can speciﬁcally classify estrogen receptor (ER), progesterone receptor (PR) and HER2/neu receptor…”
Improved classification of breast cancer by analysis of genetic alterations and gene expression profiling (2011, background): “Follow-up studies have validated some of these miRNAs (40), suggested >30 miRNAs differentiating tumor subtypes (41, 42), and defined the cell-type-specific localization of a few of these miRNAs (43).”
MicroRNAs: New Biomarkers for Diagnosis, Prognosis, Therapy Prediction and Therapeutic Tools for Breast Cancer (2015, background): “[202] tried to associate a miRNA profile with each of these genomic classes.”
The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis (2008, background): “Recently, it was reported that miR-93, another member of this family, is upregulated in basal-like breast cancer samples, associated with oestrogen receptor (ER)-negative status, and positively correlated with higher tumour grad”
miRWalk - Database: Prediction of possible miRNA binding sites by "walking" the genes of three genomes (2011, background): “In the past couple of years, research groups demonstrated the involvement of miRNAs in complicated biological processes/pathways, including the control of developmental timing, haematopoietic cell differentiation, apoptosis, cell proliferation, organ development [10,11,46,47], as well as cancerogene”
MicroRNAs in cancer: small molecules with a huge impact. (2009, background): “Further studies have investigated the correlation between microRNA expression and the classification in different subtypes of breast cancer.(56) Very recently, few groups have reported experimental evidence supporting the correlation between microRNAs and ER status: miR-206 directly targets ER , and”
Breast cancer intrinsic subtype classification, clinical use and future trends. (2015, background): “studied the miRNA expression profiling among breast malignancies classified using intrinsic subtypes, and found miR-155 differentially expressed in ER+ versus ER- tumors [57].”