title: TGFβ isoforms and receptors mRNA expression in breast tumours: prognostic value and clinical implications.
abstract: BACKGROUND
  Transforming growth factor beta (TGFβ) signalling is involved in both tumour suppression and tumour progression. The mRNA expression levels of the TGFβ isoforms and receptors in breast tumours may have prognostic value and clinical implications.
  
  
  METHODS
  The mRNA levels of TGFB1, TGFB2, TGFB3, TGFBR1 and TGFBR2 were analysed in primary breast tumours and adjacent normal breast tissues, and the associations with tumour characteristics and patients' overall and relapse-free survival were evaluated, using the public gene expression microarray data from The Cancer Genome Atlas (n = 520) and the Gene Expression Omnibus (four datasets) and our quantitative real-time PCR validation data (n = 71).
  
  
  RESULTS
  Significantly higher TGFB1 and TGFB3 mRNA levels and lower TGFBR2 mRNA levels were observed in primary tumours compared with their paired normal tissues. TGFB1 mRNA expression was seemly lower in triple-negative tumours and in tumours from lymph node-negative patients. TGFB3 mRNA expression was significantly lower in estrogen receptor-negative/progesterone receptor-negative/Basal-like/Grade 3 tumours. High TGFB2, TGFB3 and TGFBR2 mRNA levels in tumours were generally associated with better prognosis for patients, especially those diagnosed with lymph node-negative diseases. High TGFBR1 mRNA levels in tumours were associated with poorer clinical outcomes for patients diagnosed with small (diameter ≤ 2 cm) tumours.
  
  
  CONCLUSIONS
  The results indicate a reduced responsiveness of tumour cells to TGFβ, a preferential up-regulation of TGFB1 in malignant tumours and a preferential up-regulation of TGFB3 in premalignant tumours. The results may not only provide prognostic value for patients but also assist in classifying tumours according to their potential responses to TGFβ and selecting patients for TGFβ signalling pathway targeted therapies.
authors.affiliation: The University of Queensland, School of Medicine, Level 5, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane, QLD, 4102, Australia. chenfeng.chen@uqconnect.edu.au.
authors.forename: Chenfeng
authors.initials: C
authors.lastname: Chen
authors.affiliation: The University of Queensland, School of Medicine, Level 5, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane, QLD, 4102, Australia. k.zhao@uq.edu.au.
authors.forename: Kong-Nan
authors.initials: KN
authors.lastname: Zhao
authors.affiliation: The University of Queensland, School of Medicine, Level 5, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane, QLD, 4102, Australia. p.masci@uq.edu.au.
authors.forename: Paul P
authors.initials: PP
authors.lastname: Masci
authors.affiliation: The University of Queensland, School of Medicine, Level 5, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane, QLD, 4102, Australia. s.lakhani@uq.edu.au.|The University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia. s.lakhani@uq.edu.au.|Pathology Queensland, The Royal Brisbane & Women's Hospital, Brisbane, Australia. s.lakhani@uq.edu.au.
authors.forename: Sunil R
authors.initials: SR
authors.lastname: Lakhani
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia. annika.antonsson@qimr.edu.au.
authors.forename: Annika
authors.initials: A
authors.lastname: Antonsson
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia. p.simpson@uq.edu.au.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Simpson
authors.affiliation: The University of Queensland, School of Medicine, Level 5, Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane, QLD, 4102, Australia. luis.vitetta@sydney.edu.au.|Medlab Clinical, Sydney, Australia. luis.vitetta@sydney.edu.au.|The University of Sydney, Sydney Medical School, Sydney, Australia. luis.vitetta@sydney.edu.au.
authors.forename: Luis
authors.initials: L
authors.lastname: Vitetta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011379:Prognosis; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D020033:Protein Isoforms; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta