Genomic Signature of the Standardized Uptake Value in 18F-Fluorodeoxyglucose Positron Emission Tomography in Breast Cancer

Abstract

The standardized uptake value (SUV), an indicator of the degree of glucose uptake in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), has been used for predicting the clinical behavior of malignant tumors. However, its characteristics have been insufficiently explored at the genomics level. Here, we aim to identify genomic signatures reflecting prognostic SUV characteristics in breast cancer (BRC). Through integrative genomic profiling of 3710 BRC patients, including 254 patients who underwent preoperative FDG-PET, we identified an SUV signature, which showed independent clinical utility for predicting BRC prognosis (hazard ratio [HR] 1.27, 95% confidence interval [CI] = 1.12 to 1.45, p = 2.23 × 10−4). The risk subgroups classified by the signature exhibited mutually exclusive mutation patterns of TP53 and PIK3CA and showed significantly different responsiveness to immunotherapy. Experimental assays revealed that a signaling axis defined by TP53–FOXM1 and its downstream effectors in glycolysis–gluconeogenesis, including LDHA, might be important mediators in the FDG-PET process. Our molecular characterizations support an understanding of glucose metabolism and poor prognosis in BRC with a high SUV, utilizable in clinical practice to assist other diagnostic tools.

A Molecular Signature Determines the Prognostic and Therapeutic Subtype of Non-Muscle-Invasive Bladder Cancer Responsive to Intravesical Bacillus Calmette-Guérin Therapy

“…The DP.BCG+ subtype clearly showed strong alteration of cell cycle or DNA repair systems ( Figure 5 A). In this subtype, FOXM1 , TOP2A , CCNB1 , CCNB2 , and CDC25A participate in DNA repair and are activated during disease relapse [ 9 , 10 , 11 , 20 ] or play a role in the prognosis of other cancers [ 21 , 22 ], thereby supporting the poor prognostic characteristics of the DP.BCG+ subtype.…”

Relationship between tumor mutational burden and maximum standardized uptake value in 2-[18F]FDG PET (positron emission tomography) scan in cancer patients

“…Our study had several important limitations: first it is a retrospective analysis and thus TMB and SUV max parameters were not fully synchronized; second, although the full cohort included 1923 patients, only 273 patients had PET scans within 6 months before their biopsies for TMB; third, we do not know the mechanism underlying the relationship between TMB and SUV max; fourth this study was single-center/single-camera, and fifth, a variety of tumor types were included in the analysis, though the latter two may also suggest the homogeneity of PET results and generalizability of results across cancer organs, respectively); and fourth, we did not examine variant genes or molecules associated with SUV max , which could be key markers of SUV max [ 31 ] . Future studies are needed to expand the number of the patients, and to evaluate such relationship in each individual cancer type.…”

Relationship between tumor mutational burden and maximum standardized uptake value in 2-[18F]FDG PET (positron emission tomography) scan in cancer patients

“…Our study had several important limitations: rst it is a retrospective analysis and thus TMB and SUV max parameters were not fully synchronized; second, although the full cohort included 1923 patients, only 273 patients had PET scans within six months before their biopsies for TMB; third, we do not know the mechanism underlying the relationship between TMB and SUV max; fourth this study was singlecenter/single-camera, and fth, a variety of tumor types were included in the analysis, though the latter two may also suggest the homogeneity of PET results and generalizability of results across cancer organs, respectively); and fourth, we did not examine variant genes or molecules associated with SUV max , which could be key markers of SUV max [31]. Future studies are needed to expand the number of the patients, and to evaluate such relationship in each individual cancer type.…”