title: Circulating tumour cell-derived plastin3 is a novel marker for predicting long-term prognosis in patients with breast cancer.
abstract: BACKGROUND
  Identification of promising biomarkers that predict the prognosis of patients with breast cancer is needed. In this study, we hypothesised that the expression of the epithelial-mesenchymal transition-related biomarker plastin3 (PLS3) in peripheral blood could be a prognostic factor in breast cancer.
  
  
  METHODS
  We examined PLS3 expression in breast cancer cell lines with epithelial and mesenchymal traits and in circulating tumour cells (CTCs) obtained from the peripheral blood of breast cancer patients. We investigated PLS3 expression in the peripheral blood of 594 patients with breast cancer to evaluate the clinical significance of PLS3 expression.
  
  
  RESULTS
  Robust PLS3 expression was observed in different breast cancer cell lines (Hs578t, MCF-7, MDA-MB-468, and MDA-MB-231) as well as in a bone marrow derived cancer cell line (BC-M1). In both the training (n=298) and validation (n=296) sets, PLS3 expression was observed in CTCs of patients with breast cancer. PLS3-positive patients showed significantly poorer overall and disease-free survival than PLS3-negative patients (P=0.0001 and 0.003, respectively). Subset analysis revealed that this prognostic biomarker was relevant in patients with stage I-III cancer, particularly in patients with luminal-type and triple-negative-type tumours.
  
  
  CONCLUSIONS
  These data demonstrated that PLS3 was expressed in CTCs undergoing the epithelial-mesenchymal transition in patients with breast cancer. Furthermore, PLS3 may be an excellent biomarker for identifying groups at risk of recurrence or with a poor prognosis.
authors.affiliation: 1] Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan [2] Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ueo
authors.affiliation: 1] Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan [2] Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sugimachi
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
authors.forename: T M
authors.initials: TM
authors.lastname: Gorges
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Bartkowiak
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showamachi, Maebashi 371-0034, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yokobori
authors.affiliation: Department of Gynecology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Müller
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Shinden
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Department of Surgery, Ueo Breast Surgical Hospital, 188-2 Haya, Oita 870-0854, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ueo
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showamachi, Maebashi 371-0034, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kuwano
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Maehara
authors.affiliation: Department of Breast Oncology, Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka 811-1347, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ohno
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Pantel
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Mimori
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D016022:Case-Control Studies; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000097:blood*; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000097:blood*; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D012333:RNA, Messenger; C026742:plastin