Comment[ArrayExpressAccession]	E-GEOD-43040
MAGE-TAB Version	1.1								
Public Release Date	2013-06-01
Investigation Title	Integrative investigation on breast cancer in ER, PR and HER2-defined subgroups using mRNA and miRNA expression profiling and cancer core pathway analysis								
Comment[Submitted Name]	Integrative investigation on breast cancer in ER, PR and HER2-defined subgroups using mRNA and miRNA expression profiling and cancer core pathway analysis
Experiment Description	Accurate characterization and understanding of the breast cancer subtypes is of crucial clinical importance to the heterogeneity of this disease. Several layers of information, including immunohistochemical markers, mRNA and microRNA expression profiles, and pathway analysis have been used for such purpose in several studies. However, a comprehensively integrative approach is currently missing. This paper provides microRNA and mRNA expression profiles, characterizing four breast tumor subtypes, as defined by four immunohistochemical markers. The defined sets of features were validated in two independent data sets at multiple levels, including unsupervised clustering and supervised classification. Moreover, the gene expression signatures of the tumor subtypes were screened by in-depth analysis of 12 cancer core pathways. We successfully identified and validated a novel breast cancer subtypes gene expression signature composed of 976 mRNAs and 69 miRNAs. Luminal and non-luminal tumors are shown to significantly differ both at the mRNA and miRNA levels. HER2 positive tumors are more closely related to triple negative tumors by mRNA profiling than by miRNA expression. Closely related miRNAs sharing the same targets may exert opposite roles during tumor progression. Besides the core cancer pathways, other pathways such as those controling biomass synthesis are shown to be important to enable the core basal subtype with additional progressive nature compared with the other triple negative tumors. Some therapeutic strategies are proposed for breast cancer treatment, including the combined blockage of MAPK/ERK and PI3K/Pten signalings for tumors with poor clinical outcome, and targeting Wnt and JAK/STAT and/or Hedgehog, depending on tumor subtypes, together with conventional chemotherapy with the purpose of achieving an eradicative outcome. The pathway analysis also reveals that the clinical strategy and pivotal targets need to be tuned according to different tumor subtypes. This study is the first attempt to elucidate breast cancer subtypes by combining microRNA and mRNA expression, immunohistochemical markers, and cancer core pathways. The results can avail the functional studies of the etiology of breast cancer and translated for clinical use given their intrinsic link in terms of immunohistochemistry and survival. This submission consists of microRNA profiles of 115 breast cancer tumors of several subtypes only.								
Term Source Name	ArrayExpress	EFO
Term Source File	http://www.ebi.ac.uk/arrayexpress/	http://www.ebi.ac.uk/efo/efo.owl							
Person Last Name	Dai	Dai	Khan	Heikkinen	Heikkilä	Aittomäki	Blomgvist	Greco	Nevanlinna
Person First Name	Xiaofeng	Xiaofeng	Sofia	Tuomas	Päivi	Kristiina	Carl	Dario	Heli
Person Email	geo@ncbi.nlm.nih.gov								
Person Affiliation	Helsinki University Central Hospital								
Person Address	Helsinki University Central Hospital, Haartmaninkatu 8 P.O. BOX 700, Helsinki, Finland								
Person Roles	submitter								
Protocol Name	P-GSE43040-1	P-GSE43040-3	P-GSE43040-4	P-GSE43040-2	P-GSE43040-5				
Protocol Description	The data were normalised using quantile normalisation with IlluminaGUI in R ID_REF =  VALUE = quantile normalized and log2 transformed	standard Illumina protocol	Standard Illumina hybridization protocol	unknown	Standard Illumina scanning protocol				
Protocol Type	normalization data transformation protocol	labelling protocol	hybridization protocol	nucleic acid extraction protocol	array scanning protocol				
Experimental Factor Name	DISEASE SUBTYPE								
Experimental Factor Type	disease subtype								
Comment[SecondaryAccession]	GSE43040								
Comment[GEOReleaseDate]	2013-06-01								
Comment[ArrayExpressSubmissionDate]	2012-12-19								
Comment[GEOLastUpdateDate]	2013-06-02								
Comment[AEExperimentType]	transcription profiling by array								
Comment[AdditionalFile:Data1]	GSE43040_4595777022.sdf								
Comment[AdditionalFile:Data2]	GSE43040_4595777022_Metrics.txt								
Comment[AdditionalFile:Data3]	GSE43040_4595777026.sdf								
Comment[AdditionalFile:Data4]	GSE43040_4595777026_Metrics.txt								
Comment[AdditionalFile:Data5]	GSE43040_non-normalized.txt								
SDRF File	E-GEOD-43040.sdrf.txt