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Foto på Patrik Edén

Patrik Edén

Universitetslektor

Foto på Patrik Edén

Genes associated with the tumour microenvironment are differentially expressed in cured versus primary chemotherapy-refractory diffuse large B-cell lymphoma.

Författare

  • Johan Linderoth
  • Patrik Edén
  • Mats Ehinger
  • Jeanette Valcich
  • Mats Jerkeman
  • Pär-Ola Bendahl
  • Mattias Berglund
  • Gunilla Enblad
  • Martin Erlanson
  • Göran Roos
  • Eva Cavallin-Ståhl
Visa allt

Summary, in English

In order to identify genes associated with primary chemotherapy-resistance, gene expression profiles (GEP) in tumour tissue from 37 patients with de novo diffuse large B-cell lymphoma (DLBCL), stage II-IV, either in continuous complete remission (n = 24) or with progressive disease during primary treatment (n = 13), were examined using spotted 55K oligonucleotide arrays. Immunohistochemistry was used for confirmation at the protein level. The top 86 genes that best discriminated between the two cohorts were chosen for further analysis. Only seven of 86 genes were overexpressed in the refractory cohort, e.g. RABGGTB and POLE, both potential targets for drug intervention. Seventy-nine of 86 genes were overexpressed in the cured cohort and mainly coded for proteins expressed in the tumour microenvironment, many of them involved in proteolytic activity and remodelling of extra cellular matrix. Furthermore, major histocompatibility complex class I molecules, CD3D and ICAM1 were overexpressed, indicating an enhanced immunological reaction. Immunohistochemistry confirmed the GEP results. The frequency of tumour infiltrating lymphocytes, macrophages, and reactive cells expressing ICAM-1, lysozyme, cathepsin D, urokinase plasminogen activator receptor, signal transducer and activator of transcription 1, and galectin-3 was higher in the cured cohort. These findings indicate that a reactive microenvironment has an impact on the outcome of chemotherapy in DLBCL.

Avdelning/ar

  • Bröstcancer-genetik
  • Computational Biology and Biological Physics - Has been reorganised
  • Sektion V
  • Lymfom - Klinisk forskning

Publiceringsår

2008

Språk

Engelska

Sidor

423-432

Publikation/Tidskrift/Serie

British Journal of Haematology

Volym

141

Avvikelse

4

Dokumenttyp

Artikel i tidskrift

Förlag

John Wiley & Sons Inc.

Ämne

  • Hematology

Aktiv

Published

Forskningsgrupp

  • Lymphoma - Clinical Research

ISBN/ISSN/Övrigt

  • ISSN: 0007-1048