AUTHOR=Lee Hyunjong , Choi Joon Young , Joung Je-Gun , Joh Jae-Won , Kim Jong Man , Hyun Seung Hyup 

TITLE=Metabolism-Associated Gene Signatures for FDG Avidity on PET/CT and Prognostic Validation in Hepatocellular Carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.845900

DOI=10.3389/fonc.2022.845900

ISSN=2234-943X

ABSTRACT=<sec><title>Introduction</title><p>The prognostic value of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in hepatocellular carcinoma (HCC) was established in previous reports. However, there is no evidence suggesting the prognostic value of transcriptomes associated with tumor FDG uptake in HCC. It was aimed to elucidate metabolic genes and functions associated with FDG uptake, followed by assessment of those prognostic value.</p></sec><sec><title>Methods</title><p>Sixty HCC patients with Edmondson–Steiner grade II were included. FDG PET/CT scans were performed before any treatment. RNA sequencing data were obtained from tumor and normal liver tissue. Associations between each metabolism-associated gene and tumor FDG uptake were investigated by Pearson correlation analyses. A novel score between glucose and lipid metabolism-associated gene expression was calculated. In The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset, the prognostic power of selected metabolism-associated genes and a novel score was evaluated for external validation.</p></sec><sec><title>Results</title><p>Nine genes related to glycolysis and the <italic>HIF-1</italic> signaling pathway showed positive correlations with tumor FDG uptake; 21 genes related to fatty acid metabolism and the <italic>PPAR</italic> signaling pathway demonstrated negative correlations. Seven potential biomarker genes, <italic>PFKFB4</italic>, <italic>ALDOA</italic>, <italic>EGLN3</italic>, <italic>EHHADH</italic>, <italic>GAPDH</italic>, <italic>HMGCS2</italic>, and <italic>ENO2</italic> were identified. A metabolic gene expression balance score according to the dominance between glucose and lipid metabolism demonstrated good prognostic value in HCC.</p></sec><sec><title>Conclusions</title><p>The transcriptomic evidence of this study strongly supports the prognostic power of FDG PET/CT and indicates the potential usefulness of FDG PET/CT imaging biomarkers to select appropriate patients for metabolism-targeted therapy in HCC.</p></sec>