title: Gene expression profiling identifies Fibronectin 1 and CXCL9 as candidate biomarkers for breast cancer screening.
abstract: BACKGROUND
  There is a need to develop blood-based bioassays for breast cancer (BC) screening. In this study, differential gene expression between BC samples and benign tumours was used to identify candidate biomarkers for blood-based screening.
  
  
  METHODS
  We identified two proteins (Fibronectin 1 and CXCL9) from a gene expression data set that included 120 BC samples and 45 benign lesions. These proteins fulfil the following criteria: differential gene expression between cancer and benign lesion, protein released in the extracellular medium and stable in the serum, commercially available ELISA kit, ELISA accuracy in a feasibility study. Protein concentrations were determined by ELISA. Blood samples were from normal volunteers (n=119) and early BC patients (n=133).
  
  
  RESULTS
  Seventy-three per cent of patients had cT1-T2 tumour. Patients had higher CXCL9 and Fibronectin 1 concentrations than volunteers. CXCL9 mean concentration was 851 and 635 pg ml(-1) for patients and volunteers respectively (P=0.013). CXCL9 concentration was significantly higher in patients with estrogen receptor (ER)-negative compared with volunteers (P=0.003), data consistent with gene expression profile. Fibronectin 1 mean concentration was 190 microg ml(-1) for patients and 125 microg ml(-1) for volunteers (P<0.001). Areas under the curve for BC diagnosis were 0.78 and 0.62 for Fibronectin 1 and CXCL9 respectively. A combined score including Fibronectin 1 and CXCL9 dosages presented 53% of sensitivity and 98% of specificity. Similar performances were observed for ER-negative tumours.
  
  
  CONCLUSIONS
  This study suggests that Fibronectin 1/CXCL9 dosage in serum could screen a significant rate of BC, including ER-negative, and that differential gene expression analysis is a good approach to select candidate biomarkers to set up blood assays cancer screening.
authors.affiliation: Breast Cancer Translational Research Unit, UPRES EA03535, Université Paris XI, Institut Gustave Roussy, Villejuif, France.
authors.forename: E
authors.initials: E
authors.lastname: Ruiz-Garcia
authors.forename: V
authors.initials: V
authors.lastname: Scott
authors.forename: C
authors.initials: C
authors.lastname: Machavoine
authors.forename: J M
authors.initials: JM
authors.lastname: Bidart
authors.forename: L
authors.initials: L
authors.lastname: Lacroix
authors.forename: S
authors.initials: S
authors.lastname: Delaloge
authors.forename: F
authors.initials: F
authors.lastname: Andre
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis*; D054370:Chemokine CXCL9 / Q000097:blood* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005353:Fibronectins / Q000097:blood* / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C080810:CXCL9 protein, human; D054370:Chemokine CXCL9; D005353:Fibronectins; D011960:Receptors, Estrogen