MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype.
BACKGROUND
MicroRNAs (miRNAs), a class of short non-coding RNAs found in many plants and animals, often act post-transcriptionally to inhibit gene expression.


RESULTS
Here 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.


CONCLUSIONS
This 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.
Blenkiron
Cherie
C
Cancer Research UK, Cambridge Research Institute, Li Ka-Shing Centre, Robinson Way, Cambridge CB2 0RE, UK. cb391@cam.ac.uk
Goldstein
Leonard D
LD
Thorne
Natalie P
NP
Spiteri
Inmaculada
I
Chin
Suet-Feung
SF
Dunning
Mark J
MJ
Barbosa-Morais
Nuno L
NL
Teschendorff
Andrew E
AE
Green
Andrew R
AR
Ellis
Ian O
IO
Tavaré
Simon
S
Caldas
Carlos
C
Miska
Eric A
EA
D060565:Argonaute Proteins; D001943:Breast Neoplasms / Q000145:classification / Q000378:metabolism*; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D017931:DNA Primers; D004722:Endoribonucleases / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006801:Humans; D042361:Mammary Glands, Human / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D043244:Ribonuclease III
C466422:AGO2 protein, human; D060565:Argonaute Proteins; D017931:DNA Primers; D015852:Eukaryotic Initiation Factor-2; D035683:MicroRNAs; D012333:RNA, Messenger; D004722:Endoribonucleases; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases