Experiment Detail



Experiment IDEXP00124
ReferenceTitle: microRNA-associated progression pathways and potential therapeutic targetsidentified by integrated mRNA and microRNA expression profiling in breast cancer.
Author: Buffa FM, Camps C, Winchester L, Snell CE, Gee HE, Sheldon H, Taylor M, HarrisAL, Ragoussis J.
Journal: Cancer Res. 2011 Sep 1;71(17):5635-45. doi: 10.1158/0008-5472.CAN-11-0489. Epub2011 Jul 7.
Abstract: microRNA expression profiling plays an emerging role in cancer classification andidentification of therapeutic strategies. In this study, we have evaluated thebenefits of a joint microRNA-mRNA analysis in breast cancer. Matched mRNA andmicroRNA global expression profiling was conducted in a well-annotated cohort of 207 cases with complete 10-year follow-up. Penalized Cox regression includingmicroRNA expression, mRNA expression, and clinical covariates was used toidentify microRNAs associated with distant relapse-free survival (DRFS) thatprovide independent prognostic information, and are not simply surrogates ofpreviously identified prognostic covariates. Penalized regression was chosen toprevent overfitting. Furthermore, microRNA-mRNA relationships were explored byglobal expression analysis, and exploited to validate results in severalpublished cohorts (n = 592 with DRFS, n = 1,050 with recurrence-free survival).Four microRNAs were independently associated with DRFS in estrogen receptor(ER)-positive (3 novel and 1 known; miR-128a) and 6 in ER-negative (5 novel and 1known; miR-210) cases. Of the latter, miR-342, -27b, and -150 were prognosticalso in triple receptor-negative tumors. Coordinated expression of predictedtarget genes and prognostic microRNAs strengthened these results, mostsignificantly for miR-210, -128a, and -27b, whose targets were prognostic inmeta-analysis of several cohorts. In addition, miR-210 and -128a showedcoordinated expression with their cognate pri-microRNAs, which were themselvesprognostic in independent cohorts. Our integrated microRNA-mRNA global profiling approach has identified microRNAs independently associated with prognosis inbreast cancer. Furthermore, it has validated known and predicted microRNA-target interactions, and elucidated their association with key pathways that couldrepresent novel therapeutic targets.
PMID: 21737487
Expressiion ProfileDescription: microRNA expression profiling of early primary breast cancer to identify prognostic markers and associated pathways
Organism: Homo sapiens
GEO ID: GSE22216
Platform: GPL8178
Number of samples: 210
Design and SampleCancer Type: breast cancer
Cancer SubType: N/D
Cell Line: N/D
Experimental Design: subtype1 vs substype2
Case Sample: ER positive breast tumour
Control Sample: ER negative breast tumour
Num of Case: 128
Num of Control: 82
Quantification Software: Limma
Num of miRNAs: 486
IdentificationNum of Up: 87
Num of Down: 69