Breast Cancer

, Volume 21, Issue 4, pp 491–499 | Cite as

Interferon-inducible guanylate binding protein (GBP2) is associated with better prognosis in breast cancer and indicates an efficient T cell response

  • Patricio Godoy
  • Cristina Cadenas
  • Birte Hellwig
  • Rosemarie Marchan
  • Joanna Stewart
  • Raymond Reif
  • Miriam Lohr
  • Matthias Gehrmann
  • Jörg Rahnenführer
  • Markus Schmidt
  • Jan G. Hengstler
Original Article

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).

Conclusion

GBP2 is associated with better prognosis in fast proliferating tumors and probably represents a marker of an efficient T cell response.

Keywords

Breast cancer Gene arrays Inflammation GBP2 

Supplementary material

12282_2012_404_MOESM1_ESM.gif (33 kb)
Suppl. Fig. 1 (GIF 33 kb)
12282_2012_404_MOESM2_ESM.gif (37 kb)
Suppl. Fig. 2 (GIF 37 kb)
12282_2012_404_MOESM3_ESM.gif (36 kb)
Suppl. Fig. 3 (GIF 36 kb)
12282_2012_404_MOESM4_ESM.docx (20 kb)
Suppl. Table 1 (DOCX 20 kb)

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Copyright information

© The Japanese Breast Cancer Society 2012

Authors and Affiliations

  • Patricio Godoy
    • 1
  • Cristina Cadenas
    • 1
  • Birte Hellwig
    • 2
  • Rosemarie Marchan
    • 1
  • Joanna Stewart
    • 1
  • Raymond Reif
    • 1
  • Miriam Lohr
    • 2
  • Matthias Gehrmann
    • 3
  • Jörg Rahnenführer
    • 2
  • Markus Schmidt
    • 4
  • Jan G. Hengstler
    • 1
  1. 1.Leibniz Research Centre for Working Environment and Human Factors (IfADo)DortmundGermany
  2. 2.Fakultät StatistikTechnische Universität DortmundDortmundGermany
  3. 3.Bayer Technology Services GmbH, BTS-PT-AS-ATLeverkusenGermany
  4. 4.Department of GynaecologyUniversity of MainzMainzGermany

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