Table_1_Metabolism-Associated Gene Signatures for FDG Avidity on PET/CT and Prognostic Validation in Hepatocellular Carcinoma.xlsx

IntroductionThe 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.
MethodsSixty 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.
ResultsNine genes related to glycolysis and the HIF-1 signaling pathway showed positive correlations with tumor FDG uptake; 21 genes related to fatty acid metabolism and the PPAR signaling pathway demonstrated negative correlations. Seven potential biomarker genes, PFKFB4, ALDOA, EGLN3, EHHADH, GAPDH, HMGCS2, and ENO2 were identified. A metabolic gene expression balance score according to the dominance between glucose and lipid metabolism demonstrated good prognostic value in HCC.
ConclusionsThe 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.

引言
此前已有研究证实，F-18氟代脱氧葡萄糖正电子发射断层显像/计算机断层扫描（FDG PET/CT）在肝细胞癌（HCC）中的预后价值。然而，目前尚无证据表明与肿瘤FDG摄取相关的转录组在肝细胞癌中具有预后价值。本研究旨在阐明与FDG摄取相关的代谢基因及其功能，并评估其预后价值。

方法
本研究纳入60例埃德蒙森-斯坦纳分级II级的肝细胞癌患者。所有患者在接受任何治疗前均行FDG PET/CT扫描。从肿瘤组织与正常肝组织中获取RNA测序（RNA sequencing）数据。通过皮尔逊相关分析探究各代谢相关基因与肿瘤FDG摄取之间的关联。计算葡萄糖与脂质代谢相关基因表达的新型评分。在癌症基因组图谱肝细胞癌数据集（The Cancer Genome Atlas Liver Hepatocellular Carcinoma Dataset）中，对筛选出的代谢相关基因及该新型评分的预后效能进行外部验证。

结果
与糖酵解及缺氧诱导因子-1（HIF-1）信号通路相关的9个基因与肿瘤FDG摄取呈正相关；与脂肪酸代谢及过氧化物酶体增殖物激活受体（PPAR）信号通路相关的21个基因则呈负相关。本研究鉴定出7个潜在生物标志物基因：PFKFB4、ALDOA、EGLN3、EHHADH、GAPDH、HMGCS2及ENO2。基于葡萄糖与脂质代谢相对优势构建的代谢基因表达平衡评分在肝细胞癌中展现出良好的预后价值。

结论
本研究的转录组学证据有力支持了FDG PET/CT的预后价值，同时表明FDG PET/CT成像生物标志物可用于筛选适合代谢靶向治疗的肝细胞癌患者，具备潜在临床应用价值。