Cristin-resultat-ID: 949644
Sist endret: 7. februar 2013 15:26
NVI-rapporteringsår: 2012
Resultat
Vitenskapelig artikkel
2012

Hypoxia-induced gene expression in chemoradioresistant cervical cancer revealed by dynamic contrast enhanced MRI

Bidragsytere:
  • Cathinka Lønning Halle
  • Erlend K F Andersen
  • Malin Lando
  • Eva-Katrine Aarnes
  • Grete Hasvold
  • Marit Holden
  • mfl.

Tidsskrift

Cancer Research
ISSN 0008-5472
e-ISSN 1538-7445
NVI-nivå 2

Om resultatet

Vitenskapelig artikkel
Publiseringsår: 2012
Volum: 72
Hefte: 20
Sider: 5285 - 5295

Importkilder

Isi-ID: 000309972700018

Beskrivelse Beskrivelse

Tittel

Hypoxia-induced gene expression in chemoradioresistant cervical cancer revealed by dynamic contrast enhanced MRI

Sammendrag

Knowledge of the molecular background of functional magnetic resonance (MR) images is required to fully exploit their potential in cancer management. We explored the prognostic impact of dynamic contrast-enhanced MR imaging (DCE-MRI) parameters in cervical cancer combined with global gene expression data to reveal their underlying molecular phenotype and construct a representative gene signature for the relevant parameter. On the basis of 78 patients with cervical cancer subjected to curative chemoradiotherapy, we identified the prognostic DCE-MRI parameter ABrix by pharmacokinetic analysis of pretreatment images based on the Brix model, in which tumors with low ABrix appeared to be most aggressive. Gene set analysis of 46 tumors with pairwise DCE-MRI and gene expression data showed a significant correlation between ABrix and the hypoxia gene sets, whereas gene sets related to other tumor phenotypes were not significant. Hypoxia gene sets specific for cervical cancer created in cell culture experiments, including both targets of the hypoxia inducible factor (HIF1α) and the unfolded protein response, were the most significant. In the remaining 32 tumors, low ABrix was associated with upregulation of HIF1α protein expression, as assessed by immunohistochemistry, consistent with increased hypoxia. On the basis of the hypoxia gene sets, a signature of 31 genes that were upregulated in tumors with low ABrix was constructed. This DCE-MRI hypoxia gene signature showed prognostic impact in an independent validation cohort of 109 patients. Our findings reveal the molecular basis of an aggressive hypoxic phenotype and suggest the use of DCE-MRI to noninvasively identify patients with hypoxia-related chemoradioresistance.

Bidragsytere

Cathinka Halle Julin

Bidragsyterens navn vises på dette resultatet som Cathinka Lønning Halle
  • Tilknyttet:
    Forfatter
    ved Seksjon for strålingbiologi ved Oslo universitetssykehus HF

Erlend K F Andersen

  • Tilknyttet:
    Forfatter
    ved Avdeling for medisinsk fysikk ved Oslo universitetssykehus HF

Malin Lando

  • Tilknyttet:
    Forfatter
    ved Seksjon for strålingbiologi ved Oslo universitetssykehus HF

Eva-Katrine Aarnes

  • Tilknyttet:
    Forfatter
    ved Avdeling for radiologi og nukleærmedisin ved Oslo universitetssykehus HF

Grete Hasvold

  • Tilknyttet:
    Forfatter
    ved Seksjon for strålingbiologi ved Oslo universitetssykehus HF
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