title: Interferon-inducible guanylate binding protein (GBP2) is associated with better prognosis in breast cancer and indicates an efficient T cell response.
abstract: BACKGROUND
  Recently, interferon-inducible guanylate binding protein (GBP2) has been discussed as a possible control factor in tumor development, which is controlled by p53, and inhibits NF-Kappa B and Rac protein as well as expression of matrix metalloproteinase 9. However, the potential role that GBP2 plays in tumor development and prognosis has not yet been studied.
  
  
  METHODS
  We analyzed whether GBP2 mRNA levels are associated with metastasis-free interval in 766 patients with node negative breast carcinomas who did not receive systemic chemotherapy. Furthermore, response to anthracycline-based chemotherapy was studied in 768 breast cancer patients.
  
  
  RESULTS
  High expression of GBP2 in breast carcinomas was associated with better prognosis in the univariate (P < 0.001, hazard ratio 0.763, 95 % CI 0.650-0.896) as well as in the multivariate Cox analysis (P = 0.008, hazard ratio 0.731, 95 % CI 0.580-0.920) adjusted to the established clinical factors age, pT stage, grading, hormone and ERBB2 receptor status. The association was particularly strong in subgroups with high proliferation and positive estrogen receptor status but did not reach significance in carcinomas with low expression of proliferation associated genes. Besides its prognostic capacity, GBP2 also predicted pathologically complete response to anthracycline-based chemotherapy (P = 0.0037, odds ratio 1.39, 95 % CI 1.11-1.74). Interestingly, GBP2 correlated with a recently established T cell signature, indicating tumor infiltration with T cells (R = 0.607, P < 0.001).
  
  
  CONCLUSIONS
  GBP2 is associated with better prognosis in fast proliferating tumors and probably represents a marker of an efficient T cell response.
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors (IfADo), Ardeystrasse 76, 44139, Dortmund, Germany, godoy@ifado.de.
authors.forename: Patricio
authors.initials: P
authors.lastname: Godoy
authors.forename: Cristina
authors.initials: C
authors.lastname: Cadenas
authors.forename: Birte
authors.initials: B
authors.lastname: Hellwig
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Marchan
authors.forename: Joanna
authors.initials: J
authors.lastname: Stewart
authors.forename: Raymond
authors.initials: R
authors.lastname: Reif
authors.forename: Miriam
authors.initials: M
authors.lastname: Lohr
authors.forename: Matthias
authors.initials: M
authors.lastname: Gehrmann
authors.forename: Jörg
authors.initials: J
authors.lastname: Rahnenführer
authors.forename: Markus
authors.initials: M
authors.lastname: Schmidt
authors.forename: Jan G
authors.initials: JG
authors.lastname: Hengstler
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D019204:GTP-Binding Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D014408:Biomarkers, Tumor; D019204:GTP-Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C534329:GBP2 protein, human