Blood Gene Expression Profiling of Breast Cancer Survivors Experiencing Fibrosis

Journal Article · Tue Mar 01 00:00:00 EST 2011 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2010.09.052· OSTI ID:21491622

Landmark-Hoyvik, Hege ^[1]; Dumeaux, Vanessa ^[2]; Reinertsen, Kristin V ^[3]; Edvardsen, Hege ^[1]; Fossa, Sophie D ^[3]; Borresen-Dale, Anne-Lise ^[1]

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1. Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo (Norway)
2. Institute of Community Medicine, University of Tromso, Tromso (Norway)
3. Institute for Clinical Medicine, University of Oslo, Oslo (Norway)

Purpose: To extend knowledge on the mechanisms and pathways involved in maintenance of radiation-induced fibrosis (RIF) by performing gene expression profiling of whole blood from breast cancer (BC) survivors with and without fibrosis 3-7 years after end of radiotherapy treatment. Methods and Materials: Gene expression profiles from blood were obtained for 254 BC survivors derived from a cohort of survivors, treated with adjuvant radiotherapy for breast cancer 3-7 years earlier. Analyses of transcriptional differences in blood gene expression between BC survivors with fibrosis (n = 31) and BC survivors without fibrosis (n = 223) were performed using R version 2.8.0 and tools from the Bioconductor project. Gene sets extracted through a literature search on fibrosis and breast cancer were subsequently used in gene set enrichment analysis. Results: Substantial differences in blood gene expression between BC survivors with and without fibrosis were observed, and 87 differentially expressed genes were identified through linear analysis. Transforming growth factor-{beta}1 signaling was identified as the most significant gene set, showing a down-regulation of most of the core genes, together with up-regulation of a transcriptional activator of the inhibitor of fibrinolysis, Plasminogen activator inhibitor 1 in the BC survivors with fibrosis. Conclusion: Transforming growth factor-{beta}1 signaling was found down-regulated during the maintenance phase of fibrosis as opposed to the up-regulation reported during the early, initiating phase of fibrosis. Hence, once the fibrotic tissue has developed, the maintenance phase might rather involve a deregulation of fibrinolysis and altered degradation of extracellular matrix components.

• OSTI ID: 21491622
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 79, Issue 3; Other Information: DOI: 10.1016/j.ijrobp.2010.09.052; PII: S0360-3016(10)03437-1; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
BLOOD
DELAYED RADIATION EFFECTS
FIBRINOLYSIS
FIBROSIS
GENES
GROWTH FACTORS
MAMMARY GLANDS
NEOPLASMS
PLASMINOGEN
RADIOTHERAPY
SIDE EFFECTS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGICAL RADIATION EFFECTS
BLOOD COAGULATION FACTORS
BODY
BODY FLUIDS
CHEMICAL REACTIONS
DECOMPOSITION
DISEASES
DRUGS
FIBRINOLYTIC AGENTS
GLANDS
HEMATOLOGIC AGENTS
MATERIALS
MEDICINE
MITOGENS
NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
PROTEINS
PROTEOLYSIS
RADIATION EFFECTS
RADIOLOGY
THERAPY