Radiogenomic analysis of primary breast cancer reveals [18F]-fluorodeoxglucose dynamic flux-constants are positively associated with immune pathways and outperform static uptake measures in associating with glucose metabolism.

Breast Neoplasms / diagnostic imaging Female Fluorodeoxyglucose F18 Glucose Humans Kinetics Positron-Emission Tomography / methods Radiopharmaceuticals
Breast cancer FDG-PET GSEA Glycolysis/gluconeogenesis Immune pathways RNA sequencing

Journal

Breast cancer research : BCR
ISSN: 1465-542X
Titre abrégé: Breast Cancer Res
Pays: England
ID NLM: 100927353

Informations de publication

Date de publication:
17 05 2022
Historique:
received: 19 01 2022
accepted: 11 05 2022
entrez: 17 5 2022
pubmed: 18 5 2022
medline: 21 5 2022
Statut: epublish

Résumé

PET imaging of 18F-fluorodeoxygucose (FDG) is used widely for tumour staging and assessment of treatment response, but the biology associated with FDG uptake is still not fully elucidated. We therefore carried out gene set enrichment analyses (GSEA) of RNA sequencing data to find KEGG pathways associated with FDG uptake in primary breast cancers. Pre-treatment data were analysed from a window-of-opportunity study in which 30 patients underwent static and dynamic FDG-PET and tumour biopsy. Kinetic models were fitted to dynamic images, and GSEA was performed for enrichment scores reflecting Pearson and Spearman coefficients of correlations between gene expression and imaging. A total of 38 pathways were associated with kinetic model flux-constants or static measures of FDG uptake, all positively. The associated pathways included glycolysis/gluconeogenesis ('GLYC-GLUC') which mediates FDG uptake and was associated with model flux-constants but not with static uptake measures, and 28 pathways related to immune-response or inflammation. More pathways, 32, were associated with the flux-constant K of the simple Patlak model than with any other imaging index. Numbers of pathways categorised as being associated with individual micro-parameters of the kinetic models were substantially fewer than numbers associated with flux-constants, and lay around levels expected by chance. In pre-treatment images GLYC-GLUC was associated with FDG kinetic flux-constants including Patlak K, but not with static uptake measures. Immune-related pathways were associated with flux-constants and static uptake. Patlak K was associated with more pathways than were the flux-constants of more complex kinetic models. On the basis of these results Patlak analysis of dynamic FDG-PET scans is advantageous, compared to other kinetic analyses or static imaging, in studies seeking to infer tumour-to-tumour differences in biology from differences in imaging. Trial registration NCT01266486, December 24th 2010.

Sections du résumé

BACKGROUND
PET imaging of 18F-fluorodeoxygucose (FDG) is used widely for tumour staging and assessment of treatment response, but the biology associated with FDG uptake is still not fully elucidated. We therefore carried out gene set enrichment analyses (GSEA) of RNA sequencing data to find KEGG pathways associated with FDG uptake in primary breast cancers.
METHODS
Pre-treatment data were analysed from a window-of-opportunity study in which 30 patients underwent static and dynamic FDG-PET and tumour biopsy. Kinetic models were fitted to dynamic images, and GSEA was performed for enrichment scores reflecting Pearson and Spearman coefficients of correlations between gene expression and imaging.
RESULTS
A total of 38 pathways were associated with kinetic model flux-constants or static measures of FDG uptake, all positively. The associated pathways included glycolysis/gluconeogenesis ('GLYC-GLUC') which mediates FDG uptake and was associated with model flux-constants but not with static uptake measures, and 28 pathways related to immune-response or inflammation. More pathways, 32, were associated with the flux-constant K of the simple Patlak model than with any other imaging index. Numbers of pathways categorised as being associated with individual micro-parameters of the kinetic models were substantially fewer than numbers associated with flux-constants, and lay around levels expected by chance.
CONCLUSIONS
In pre-treatment images GLYC-GLUC was associated with FDG kinetic flux-constants including Patlak K, but not with static uptake measures. Immune-related pathways were associated with flux-constants and static uptake. Patlak K was associated with more pathways than were the flux-constants of more complex kinetic models. On the basis of these results Patlak analysis of dynamic FDG-PET scans is advantageous, compared to other kinetic analyses or static imaging, in studies seeking to infer tumour-to-tumour differences in biology from differences in imaging. Trial registration NCT01266486, December 24th 2010.

Identifiants

DOI: 10.1186/s13058-022-01529-9 PMID: 35581637 PMC: PMC9115966
pubmed: 35581637
doi: 10.1186/s13058-022-01529-9
pii: 10.1186/s13058-022-01529-9
pmc: PMC9115966
doi:

Substances chimiques

Radiopharmaceuticals 0
Fluorodeoxyglucose F18 0Z5B2CJX4D
Glucose IY9XDZ35W2

Banques de données

ClinicalTrials.gov
['NCT01266486']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

34

Informations de copyright

© 2022. The Author(s).

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Auteurs

G P Ralli (GP)

Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.

R D Carter (RD)

Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Doctoral Training Centre, University of Oxford, Keble Road, Oxford, OX1 3NP, UK.
Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Road, Oxford, OX1 3PT, UK.

D R McGowan (DR)

Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK. daniel.mcgowan@oncology.ox.ac.uk.
Department of Medical Physics and Clinical Engineering, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Oxford, OX3 7LE, UK. daniel.mcgowan@oncology.ox.ac.uk.

W-C Cheng (WC)

Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.

D Liu (D)

Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.

E J Teoh (EJ)

Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Department of Nuclear Medicine, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Oxford, OX3 7LE, UK.
Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.

N Patel (N)

Department of Nuclear Medicine, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Oxford, OX3 7LE, UK.

F Gleeson (F)

Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Department of Nuclear Medicine, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Oxford, OX3 7LE, UK.

A L Harris (AL)

Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.

S R Lord (SR)

Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK.

F M Buffa (FM)

Department of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.

J D Fenwick (JD)

Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Daulby Street, Liverpool, L69 3GA, UK.

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Classifications MeSH

questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Maladies du sein › Tumeurs du sein › Radiogenomic analysis of primary breast cancer...
questionsmedicales.fr › Glucides › Désoses › Désoxyglucose › Fluorodésoxyglucose F18 › Radiogenomic analysis of primary breast cancer...
questionsmedicales.fr › Glucides › Sucres › Oses › Hexose › Glucose › Radiogenomic analysis of primary breast cancer...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Radiogenomic analysis of primary breast cancer...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Cinétique › Radiogenomic analysis of primary breast cancer...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Techniques de diagnostic radioisotopique › Scintigraphie › Tomoscintigraphie › Tomographie par émission de positons › Radiogenomic analysis of primary breast cancer...
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Produits chimiques de laboratoire › Indicateurs et réactifs › Radiopharmaceutiques › Radiogenomic analysis of primary breast cancer...