miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients
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The proper validation of prognostic biomarkers is an important clinical issue in breast cancer research. MicroRNAs (miRNAs) have emerged as a new class of promising breast cancer biomarkers. In the present work, we developed an integrated online bioinformatic tool to validate the prognostic relevance of miRNAs in breast cancer.
A database was set up by searching the GEO, EGA, TCGA, and PubMed repositories to identify datasets with published miRNA expression and clinical data. Kaplan–Meier survival analysis was performed to validate the prognostic value of a set of 41 previously published survival-associated miRNAs.
All together 2178 samples from four independent datasets were integrated into the system including the expression of 1052 distinct human miRNAs. In addition, the web-tool allows for the selection of patients, which can be filtered by receptors status, lymph node involvement, histological grade, and treatments. The complete analysis tool can be accessed online at: www.kmplot.com/mirpower. We used this tool to analyze a large number of deregulated miRNAs associated with breast cancer features and outcome, and confirmed the prognostic value of 26 miRNAs. A significant correlation in three out of four datasets was validated only for miR-29c and miR-101.
In summary, we established an integrated platform capable to mine all available miRNA data to perform a survival analysis for the identification and validation of prognostic miRNA markers in breast cancer.
KeywordsBreast cancer Biomarkers MicroRNAs Gene expression Prognosis Survival
This study was supported by the Hungarian Scientific Research Fund (OTKA) K 108655 Grant (to B.G.), Associazione Italiana Ricerca sul Cancro (Grant 6251 to L.S.), and Fondazione Italiana Ricerca sul Cancro (FIRC fellowship 18328 to G.B.). The authors are grateful to Laura Paladini for her cooperation in data collection.
B.G. and L.S. conceived, designed, and supervised the study. B.G., A.L., A.N., and L.S. performed the analysis. G.B., B.G., G.M., and L.S. reviewed the literature. G.B., B.G., A.L., A.N., L.S., and A.S. participated in data interpretation. All authors were involved in writing and reviewing the manuscript, and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 2.Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann B, Senn HJ (2013) Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 24:2206–2223. doi: 10.1093/annonc/mdt303 CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Blenkiron C, Goldstein LD, Thorne NP, Spiteri I, Chin SF, Dunning MJ, Barbosa-Morais NL, Teschendorff AE, Green AR, Ellis IO, Tavaré S, Caldas C, Miska EA (2007) MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype. Genome Biol 8:R214. doi: 10.1186/gb-2007-8-10-r214 CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Ménard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM (2005) MicroRNA gene expression deregulation in human breast cancer. Cancer Res 65:7065–7070. doi: 10.1158/0008-5472.CAN-05-1783 CrossRefPubMedGoogle Scholar
- 7.Buffa FM, Camps C, Winchester L, Snell CE, Gee HE, Sheldon H, Taylor M, Harris AL, Ragoussis J (2011) microRNA-associated progression pathways and potential therapeutic targets identified by integrated mRNA and microRNA expression profiling in breast cancer. Cancer Res 71:5635–5645. doi: 10.1158/0008-5472.CAN-11-0489 CrossRefPubMedGoogle Scholar
- 9.van Schooneveld E, Wildiers H, Vergote I, Vermeulen PB, Dirix LY, Van Laere SJ (2015) Dysregulation of microRNAs in breast cancer and their potential role as prognostic and predictive biomarkers in patient management. Breast Cancer Res 17:21. doi: 10.1186/s13058-015-0526-y CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Dvinge H, Git A, Gräf S, Salmon-Divon M, Curtis C, Sottoriva A, Zhao Y, Hirst M, Armisen J, Miska EA, Chin SF, Provenzano E, Turashvili G, Green A, Ellis I, Aparicio S, Caldas C (2013) The shaping and functional consequences of the microRNA landscape in breast cancer. Nature 497:378–382. doi: 10.1038/nature12108 CrossRefPubMedGoogle Scholar
- 13.de Rinaldis E, Gazinska P, Mera A, Modrusan Z, Fedorowicz GM, Burford B, Gillett C, Marra P, Grigoriadis A, Dornan D, Holmberg L, Pinder S, Tutt A (2013) Integrated genomic analysis of triple-negative breast cancers reveals novel microRNAs associated with clinical and molecular phenotypes and sheds light on the pathways they control. BMC Genom 23(14):643. doi: 10.1186/1471-2164-14-643 CrossRefGoogle Scholar
- 14.Enerly E, Steinfeld I, Kleivi K, Leivonen SK, Aure MR, Russnes HG, Rønneberg JA, Johnsen H, Navon R, Rødland E, Mäkelä R, Naume B, Perälä M, Kallioniemi O, Kristensen VN, Yakhini Z, Børresen-Dale AL (2011) miRNA-mRNA integrated analysis reveals roles for miRNAs in primary breast tumors. PLoS One 6:e16915. doi: 10.1371/journal.pone.0016915 CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Györffy B, Lanczky A, Eklund AC, Denkert C, Budczies J, Li Q, Szallasi Z (2010) An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1809 patients. Breast Cancer Res Treat 123:725–731. doi: 10.1007/s10549-009-0674-9 CrossRefPubMedGoogle Scholar
- 23.De Mattos-Arruda L, Bottai G, Nuciforo PG, Di Tommaso L, Giovannetti E, Peg V, Losurdo A, Pérez-Garcia J, Masci G, Corsi F, Cortés J, Seoane J, Calin GA, Santarpia L (2015) MicroRNA-21 links epithelial-to-mesenchymal transition and inflammatory signals to confer resistance to neoadjuvant trastuzumab and chemotherapy in HER2-positive breast cancer patients. Oncotarget 6:37269–37280. doi: 10.18632/oncotarget.5495 PubMedPubMedCentralGoogle Scholar
- 24.Parrella P, Barbano R, Pasculli B, Fontana A, Copetti M, Valori VM, Poeta ML, Perrone G, Righi D, Castelvetere M, Coco M, Balsamo T, Morritti M, Pellegrini F, Onetti-Muda A, Maiello E, Murgo R, Fazio VM (2014) Evaluation of microRNA-10b prognostic significance in a prospective cohort of breast cancer patients. Mol Cancer 13:142. doi: 10.1186/1476-4598-13-142 CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Song SJ, Poliseno L, Song MS, Ala U, Webster K, Ng C, Beringer G, Brikbak NJ, Yuan X, Cantley LC, Richardson AL, Pandolfi PP (2013) MicroRNA-antagonism regulates breast cancer stemness and metastasis via TET-family-dependent chromatin remodeling. Cell 154:311–324. doi: 10.1016/j.cell.2013.06.026 CrossRefPubMedPubMedCentralGoogle Scholar