Standardized uptake value (SUV), an indicator of the glucose uptake degree in 18F-fluorodeoxy-glucose positron emission tomography (FDG-PET), has been used as a prognostic factor in various malignant tumors. The aim of this study is to identify a molecular signature reflecting prognostic SUV characteristics in breast cancer (BRC).
We sought to identify a molecular signature associated with SUV by a gene expression profiling using a dataset obtained from 60 BRCs who underwent preoperative FDG-PET. The prognostic value of the signature was verified in three BRC cohorts including TCGA dataset (n = 1,616). Various statistical methods, including log-rank and Cox regression analyses, were applied to estimate an association between the signature and BRC prognosis. To compare somatic variants between two patient subgroups divided by the signature, we obtained predefined gene sets involved in oncogenic or metabolic pathways and estimated a difference of their mutation frequencies between subgroups in the TCGA cohort.
By a gene expression profiling, we defined a signature, namely SUV signature, consisting of 723 genes significantly associated with SUV (Pearson correlation test, |r| > 0.35, p < 0.001). The patient subgroups classified by the signature [i.e., SUV-high-cluster and SUV-low-cluster] were significantly similar with patient classification by SUV [Fisher exact test, odds ratio 8.02, 95% confidence interval (CI) = 2.45-29.3, p < 0.001]. When estimating prognostic value of the SUV signature in three cohorts, the signature showed a strong prediction ability (log-rank tests, each p < 0.05) and an independent clinical utility (multivariate Cox regression model, hazard ratio = 1.51, 95% CI = 1.07-2.22, p = 0.01) in BRC prognosis. Gene network and mutation analyses revealed that a signaling defined by TP53-FOXM1 and its downstream effectors involved in glycolysis-gluconeogenesis might be important mediators in FDG-PET operation.
Our results uncover genomic and metabolomic characteristics of glucose uptake captured by FDG-PET, supporting an understanding of glucose metabolism as well as a poor prognosis in BRC patients with high SUV.
Clinical trial identification
Legal entity responsible for the study
Korea Research Institute of Bioscience and Biotechnology Gananam Severance Hospital.
Korea Research Institute of Bioscience and Biotechnology.
All authors have declared no conflicts of interest.