title: Proteomic analyses reveal high expression of decorin and endoplasmin (HSP90B1) are associated with breast cancer metastasis and decreased survival.
abstract: BACKGROUND
  Breast cancer is the most common malignancy among women worldwide in terms of incidence and mortality. About 10% of North American women will be diagnosed with breast cancer during their lifetime and 20% of those will die of the disease. Breast cancer is a heterogeneous disease and biomarkers able to correctly classify patients into prognostic groups are needed to better tailor treatment options and improve outcomes. One powerful method used for biomarker discovery is sample screening with mass spectrometry, as it allows direct comparison of protein expression between normal and pathological states. The purpose of this study was to use a systematic and objective method to identify biomarkers with possible prognostic value in breast cancer patients, particularly in identifying cases most likely to have lymph node metastasis and to validate their prognostic ability using breast cancer tissue microarrays.
  
  
  RESULTS
  Differential proteomic analyses were employed to identify candidate biomarkers in primary breast cancer patients. These analyses identified decorin (DCN) and endoplasmin (HSP90B1) which play important roles regulating the tumour microenvironment and in pathways related to tumorigenesis. This study indicates that high expression of Decorin is associated with lymph node metastasis (p<0.001), higher number of positive lymph nodes (p<0.0001) and worse overall survival (p = 0.01). High expression of HSP90B1 is associated with distant metastasis (p<0.0001) and decreased overall survival (p<0.0001) these patients also appear to benefit significantly from hormonal treatment.
  
  
  CONCLUSIONS
  Using quantitative proteomic profiling of primary breast cancers, two new promising prognostic and predictive markers were found to identify patients with worse survival. In addition HSP90B1 appears to identify a group of patients with distant metastasis with otherwise good prognostic features.
authors.affiliation: Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Cawthorn
authors.forename: Juan C
authors.initials: JC
authors.lastname: Moreno
authors.forename: Moyez
authors.initials: M
authors.lastname: Dharsee
authors.forename: Danh
authors.initials: D
authors.lastname: Tran-Thanh
authors.forename: Suzanne
authors.initials: S
authors.lastname: Ackloo
authors.forename: Pei Hong
authors.initials: PH
authors.lastname: Zhu
authors.forename: Girish
authors.initials: G
authors.lastname: Sardana
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Peter
authors.initials: P
authors.lastname: Kupchak
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Jacks
authors.forename: Naomi A
authors.initials: NA
authors.lastname: Miller
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Youngson
authors.forename: Vladimir
authors.initials: V
authors.lastname: Iakovlev
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Guidos
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Vallis
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Evans
authors.forename: David
authors.initials: D
authors.lastname: McCready
authors.forename: Wey L
authors.initials: WL
authors.lastname: Leong
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Done
mesh_terms: D000595:Amino Acid Sequence; D000912:Antibodies, Neoplasm / Q000276:immunology; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D058575:Decorin / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology; D013058:Mass Spectrometry; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results
chemical_list: D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor; D058575:Decorin; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D010455:Peptides; C053387:endoplasmin