Refinement of breast cancer molecular classification by miRNA expression profiles

• Published in: BMC genomics Vol. 20; no. 1; p. 503
• Main Authors: Søkilde, Rolf, Persson, Helena, Ehinger, Anna, Pirona, Anna Chiara, Fernö, Mårten, Hegardt, Cecilia, Larsson, Christer, Loman, Niklas, Malmberg, Martin, Rydén, Lisa, Saal, Lao, Borg, Åke, Vallon-Christerson, Johan, Rovira, Carlos
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 17.06.2019; BioMed Central; BMC
• Subjects: Analysis; Basic Medicine; Biochemistry; Bioinformatics; Biomarkers; Breast cancer; Breast Neoplasms - classification; Breast Neoplasms - genetics; Cancer and Oncology; Cancer genetics; Cancer och onkologi; Cell and Molecular Biology; Cell- och molekylärbiologi; Classification; Clinical Medicine; Cluster Analysis; Clusters; Cohort Studies; Computational Biology - methods; Differential expression; Discovery tools; ErbB-2 protein; Gene expression; Gene Expression Profiling; Genes; Genetic aspects; Genetic markers; Genomics; Humans; Identification and classification; Klinisk medicin; LINC00478; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Messenger RNA; MicroRNA; MicroRNAs; MicroRNAs - genetics; Mir-4728; miR-99a/let-7c/miR-125b; miRNA; Non-coding RNA; Prognosis; Ribonucleic acid; RNA; Studies; Tumors; Unsupervised Machine Learning; Sweden; Molecular subtypes; Mir-4728; miR-99a/let-7c/miR-125b; microRNA; Breast cancer; Differential expression; Non-coding RNA; LINC00478
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/s12864-019-5887-7

Accurate classification of breast cancer using gene expression profiles has contributed to a better understanding of the biological mechanisms behind the disease and has paved the way for better prognostication and treatment prediction. We found that miRNA profiles largely recapitulate intrinsic subtypes. In the case of HER2-enriched tumors a small set of miRNAs including the HER2-encoded mir-4728 identifies the group with very high specificity. We also identified differential expression of the miR-99a/let-7c/miR-125b miRNA cluster as a marker for separation of the Luminal A and B subtypes. High expression of this miRNA cluster is linked to better overall survival among patients with Luminal A tumors. Correlation between the miRNA cluster and their precursor LINC00478 is highly significant suggesting that its expression could help improve the accuracy of present day's signatures. We show here that miRNA expression can be translated into mRNA profiles and that the inclusion of miRNA information facilitates the molecular diagnosis of specific subtypes, in particular the clinically relevant sub-classification of luminal tumors.