title: LSD1 overexpression is associated with poor prognosis in basal-like breast cancer, and sensitivity to PARP inhibition.
abstract: LSD1, a lysine-specific histone demethylase, is overexpressed in several types of cancers and linked to poor outcomes. In breast cancer, the significance of LSD1 overexpression is not clear. We have performed an in silico analysis to assess the relationship of LSD1 expression to clinical outcome. We demonstrate that LSD1 overexpression is a poor prognostic factor in breast cancer, especially in basal-like breast cancer, a subtype of breast cancer with aggressive clinical features. This link is also observed in samples of triple negative breast cancer. Interestingly, we note that overexpression of LSD1 correlates with down-regulation of BRCA1 in triple negative breast cancer. This phenomenon is also observed in in vitro models of basal-like breast cancer, and is associated with an increased sensitivity to PARP inhibitors. We propose therefore that high expression levels of the demethylase LSD1 is a potential prognostic factor of poor outcome in basal-like breast cancer, and that PARP inhibition may be a therapeutic strategy of interest in this poor prognostic subtype with overexpression of LSD1.
authors: Department of Translational Oncology, St. Marianna University Graduate School of Medicine, Kawasaki, 216-8511, Japan; Division of Breast and Endocrine Surgery, Department of Surgery, St. Marianna University School of Medicine, Kawasaki, 216-8511, Japan.
authors: Satoi
authors: S
authors: Nagasawa
authors: Department of Translational Oncology, St. Marianna University Graduate School of Medicine, Kawasaki, 216-8511, Japan.
authors: Anna S
authors: AS
authors: Sedukhina
authors: Department of Translational Oncology, St. Marianna University Graduate School of Medicine, Kawasaki, 216-8511, Japan; Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, Kawasaki, 216-8511, Japan.
authors: Yuko
authors: Y
authors: Nakagawa
authors: Department of Pathology, St. Marianna University School of Medicine, Kawasaki, 216-8511, Japan.
authors: Ichiro
authors: I
authors: Maeda
authors: Department of Pathology, St. Marianna University School of Medicine, Kawasaki, 216-8511, Japan.
authors: Manabu
authors: M
authors: Kubota
authors: Department of Pathology, St. Marianna University School of Medicine, Kawasaki, 216-8511, Japan.
authors: Shigeko
authors: S
authors: Ohnuma
authors: Division of Breast and Endocrine Surgery, Department of Surgery, St. Marianna University School of Medicine, Kawasaki, 216-8511, Japan.
authors: Koichiro
authors: K
authors: Tsugawa
authors: Department of Translational Oncology, St. Marianna University Graduate School of Medicine, Kawasaki, 216-8511, Japan.
authors: Tomohiko
authors: T
authors: Ohta
authors: Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/Melchor Fernandez Almagro 3, 28029, Madrid, Spain.
authors: Marta
authors: M
authors: Roche-Molina
authors: Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/Melchor Fernandez Almagro 3, 28029, Madrid, Spain.
authors: Juan A
authors: JA
authors: Bernal
authors: University of Cambridge, The Medical Research Council Cancer Cell Unit, Hutchison/MRC Research Centre, Hills Road, Cambridge, CB2 OXZ, United Kingdom.
authors: Ana J
authors: AJ
authors: Narváez
authors: Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, 14 Medical Drive, #12-01, Singapore, 117599, Singapore.
authors: Anand D
authors: AD
authors: Jeyasekharan
authors: Department of Translational Oncology, St. Marianna University Graduate School of Medicine, Kawasaki, 216-8511, Japan.
authors: Ko
authors: K
authors: Sato
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D045744:Cell Line, Tumor; D019295:Computational Biology / Q000379:methods; D030541:Databases, Genetic; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D056466:Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D018295:Neoplasms, Basal Cell / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology*; D011379:Prognosis; D012333:RNA, Messenger; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000401:mortality
chemical_list: D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012333:RNA, Messenger; D056466:Histone Demethylases; C495195:KDM1A protein, human