title: Common profiles of Notch signaling differentiate disease-free survival in luminal type A and triple negative breast cancer.
abstract: Breast cancer (BC) is characterized by high heterogeneity regarding its biology and clinical characteristics. The Notch pathway regulates such processes as organ modeling and epithelial-to-mesenchymal transition (EMT).The aim of the study was to determine the effect of differential expression of Notch members on disease-free survival (DFS) in luminal type A (lumA) and triple negative (TN) BC.The differential expression of 19 Notch members was examined in a TCGA BC cohort. DFS analysis was performed using the log-rank test (p<0.05). Biological differences between DFS groups were determined with Gene Set Enrichment Analysis (GSEA) (tTest, FDR<0.25). Common expression profiles according to Notch signaling were examined using ExpressCluster (K-means, mean centered, Euclidean distance metric).The overexpression of HES1, LFNG and PSEN1 was found to be favorable for DFS in lumA, and lowered expression favorable for DFS in TN.GSEA analysis showed that differential Notch signaling is associated with cell cycle, tissue architecture and remodeling. Particularly, targets of E2F, early stage S phase transcription factor, were upregulated in the lumA unfavorable group and the TN favorable group differentiated on a basis of HES1 and PSEN1 expression.Summarizing, our analysis show significance of Notch signaling in BRCA progression through triggering EMT. Moreover, identification of numerous genes which overexpression is associated with disease recurrence may serve as a source of potential targets for a new anticancer therapy.
authors.affiliation: Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz, 90-752, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Orzechowska
authors.affiliation: Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz, 90-752, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Jędroszka
authors.affiliation: Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz, 90-752, Poland.
authors.forename: Andrzej K
authors.initials: AK
authors.lastname: Bednarek
mesh_terms: D045744:Cell Line, Tumor; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D016695:Glycosyltransferases / Q000235:genetics; D006801:Humans; D053764:Presenilin-1 / Q000235:genetics; D011379:Prognosis; D051880:Receptors, Notch / Q000235:genetics*; D015398:Signal Transduction; D000072056:Transcription Factor HES-1 / Q000235:genetics; D064726:Triple Negative Breast Neoplasms / Q000235:genetics*
chemical_list: C508853:PSEN1 protein, human; D053764:Presenilin-1; D051880:Receptors, Notch; D000072056:Transcription Factor HES-1; C078493:HES1 protein, human; D016695:Glycosyltransferases; C498393:LFNG protein, human
keywords: Notch; breast neoplasms; disease-free survival; epithelial-to-mesenchymal transition