Experiment ID | EXP00126 |
Reference | Title: 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 Profile | Description: 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 Sample | Cancer Type: breast cancer Cancer SubType: N/D Cell Line: N/D Experimental Design: high grade vs low grade Case Sample: breast tumor grade 3 Control Sample: breast tumor grade 1 Num of Case: 63 Num of Control: 42 Quantification Software: Limma Num of miRNAs: 486 |
Identification | Num of Up: 67 Num of Down: 97 |