Ralli, GP;
Carter, RD;
McGowan, DR;
Cheng, WC;
Liu, D;
Teoh, EJ;
Patel, N;
... Fenwick, JD; + view all
(2022)
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 Cancer Research
, 24
(1)
, Article 34. 10.1186/s13058-022-01529-9.
Preview |
Text
Radiogenomic analysis of primary breast cancer reveals [18F]-fluorodeoxglucose dynamic flux-constants are positively associa.pdf - Other Download (3MB) | Preview |
Abstract
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.
| Type: | Article |
|---|---|
| Title: | 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 |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s13058-022-01529-9 |
| Publisher version: | https://doi.org/10.1186/s13058-022-01529-9 |
| Language: | English |
| Additional information: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
| Keywords: | Breast cancer, FDG-PET, GSEA, Glycolysis/gluconeogenesis, Immune pathways, RNA sequencing, Breast Neoplasms, Female, Fluorodeoxyglucose F18, Glucose, Humans, Kinetics, Positron-Emission Tomography, Radiopharmaceuticals |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10161406 |
Archive Staff Only
 |
View Item |
