title: Integrated MicroRNA-mRNA Profiling Identifies Oncostatin M as a Marker of Mesenchymal-Like ER-Negative/HER2-Negative Breast Cancer.
abstract: MicroRNAs (miRNAs) simultaneously modulate different oncogenic networks, establishing a dynamic system of gene expression and pathway regulation. In this study, we analyzed global miRNA and messenger RNA (mRNA) expression profiles of 17 cell lines representing different molecular breast cancer subtypes. Spearman's rank correlation test was used to evaluate the correlation between miRNA and mRNA expression. Hierarchical clustering and pathway analysis were also performed. Publicly available gene expression profiles (n= 699) and tumor tissues (n= 80) were analyzed to assess the relevance of key miRNA-regulated pathways in human breast cancer. We identified 39 significantly deregulated miRNAs, and the integration between miRNA and mRNA data revealed the importance of immune-related pathways, particularly the Oncostatin M (OSM) signaling, associated with mesenchymal-like breast cancer cells. OSM levels correlated with genes involved in the inflammatory response, epithelial-to-mesenchymal transition (EMT), and epidermal growth factor (EGF) signaling in human estrogen receptor (ER)-negative/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Our results suggest that the deregulation of specific miRNAs may cooperatively impair immune and EMT pathways. The identification of the OSM inflammatory pathway as an important mediator of EMT in triple-negative breast cancer (TNBC) may provide a novel potential opportunity to improve therapeutic strategies.
authors.affiliation: Oncology Experimental Therapeutics, Humanitas Clinical and Research Institute, 20089 Rozzano-Milan, Italy. giulia.bottai@humanitasresearch.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Bottai
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. ldiao@mdanderson.org.
authors.forename: Lixia
authors.initials: L
authors.lastname: Diao
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. kabagger@mdanderson.org.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Baggerly
authors.affiliation: Oncology Experimental Therapeutics, Humanitas Clinical and Research Institute, 20089 Rozzano-Milan, Italy. laura.paladini@humanitasresearch.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Paladini
authors.affiliation: 2nd Department of Pediatrics, Semmelweis University, H-1094 Budapest, Hungary. gyorffy.balazs@ttk.mta.hu.|MTA TTK Lendület Cancer Biomarker Research Group, Hungarian Academy of Sciences, H-1117 Budapest, Hungary. gyorffy.balazs@ttk.mta.hu.
authors.forename: Balázs
authors.initials: B
authors.lastname: Győrffy
authors.affiliation: Oncology Experimental Therapeutics, Humanitas Clinical and Research Institute, 20089 Rozzano-Milan, Italy. carlotta.raschioni@humanitas.it.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Raschioni
authors.affiliation: Department of Breast Medical Oncology, Yale University, Yale Cancer Center, New Haven, CT 06520, USA. lajos.pusztai@yale.edu.
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. gcalin@mdanderson.org.|RNA Interference and Non-Coding RNA Center, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. gcalin@mdanderson.org.
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
authors.affiliation: Oncology Experimental Therapeutics, Humanitas Clinical and Research Institute, 20089 Rozzano-Milan, Italy. libero.santarpia@humanitasresearch.it.
authors.forename: Libero
authors.initials: L
authors.lastname: Santarpia
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008648:Mesoderm / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D053683:Oncostatin M / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D059467:Transcriptome; D064726:Triple Negative Breast Neoplasms / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D053683:Oncostatin M; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen
keywords: Oncostatin M; breast cancer; immune response; microRNAs; molecular subtypes