Jia Wenzhi, Wu Qianyun, Yu Xiaofeng, Shen Mengqin, Zhang Ruixue, Li Jiajin, Zhao Li, Huang Gang, Liu Jianjun
Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Front Oncol. 2022 Dec 8;12:1044902. doi: 10.3389/fonc.2022.1044902. eCollection 2022.
The glycolytic enzyme fructose 1,6-bisphosphate aldolase B (ALDOB) is aberrantly expressed and impacts the prognosis in hepatocellular carcinoma (HCC). Hepatic ALDOB loss leads to paradoxical upregulation of glucose metabolism, favoring hepatocellular carcinogenesis. Nevertheless, the relationship between ALDOB expression and F-fluorodeoxyglucose (F-FDG) uptake, and their effects on HCC prognosis remain unclear. We evaluated whether ALDOB expression is associated with F-FDG uptake and their impacts on HCC prognosis prediction.
Changes in ALDOB expression levels and the prognostic values in HCC were analyzed using data from The Cancer Genome Atlas (TCGA) database. Ultimately, 34 patients with HCC who underwent F-FDG positron emission tomography/computed tomography (PET/CT) preoperatively were enrolled in this retrospective study. ALDOB expression was determined using immunohistochemistry (IHC) staining, and the maximum standardized uptake value (SUVmax) of HCC was calculated from the F-FDG PET/CT scans. The relationship between ALDOB expression and SUVmax was examined, and their impacts on overall survival were evaluated using Cox proportional hazards models and Kaplan-Meier survival analysis. ALDOB overexpression in HUH7 and 7721 cells was used to analyze its role in tumor metabolism.
According to TCGA database, the ALDOB mRNA level was downregulated in HCC compared to normal tissue, and significantly shortened overall survival in HCC patients. ALDOB protein expression was similarly decreased in IHC findings in HCC than that in adjacent normal tissues (P<0.05) and was significantly associated with tumor size (P<0.001), high tumor-node-metastasis stage (P=0.022), and elevated SUVmax (P=0.009). ALDOB expression in HCC was inversely correlated with SUVmax (r=-0.454; P=0.012), and the optimal SUVmax cutoff value for predicting its expression was 4.15. Prognostically, low ALDOB expression or SUVmax ≥3.9 indicated shorter overall survival time in HCC. Moreover, COX regression analysis suggested high SUVmax as an independent prognostic risk factor for HCC (P=0.036). HCC patients with negative ALDOB expression and positive SUVmax (≥3.9) were correlated with worse prognosis. ALDOB overexpression in HCC cells significantly decreases F-FDG uptake and lactate production.
SUVmax in HCC patients is inversely correlated with ALDOB expression, and F-FDG PET/CT may be useful for ALDOB status prediction. The combined use of ALDOB expression and F-FDG PET/CT data can provide additional information on disease prognosis in HCC patients.
糖酵解酶果糖1,6 - 二磷酸醛缩酶B（ALDOB）在肝细胞癌（HCC）中异常表达并影响预后。肝脏中ALDOB缺失导致葡萄糖代谢的反常上调，有利于肝细胞癌的发生。然而，ALDOB表达与氟代脱氧葡萄糖（F-FDG）摄取之间的关系及其对HCC预后的影响仍不清楚。我们评估了ALDOB表达是否与F-FDG摄取相关及其对HCC预后预测的影响。
使用来自癌症基因组图谱（TCGA）数据库的数据，分析HCC中ALDOB表达水平的变化及其预后价值。最终，34例术前接受F-FDG正电子发射断层扫描/计算机断层扫描（PET/CT）的HCC患者纳入本回顾性研究。采用免疫组织化学（IHC）染色测定ALDOB表达，并从F-FDG PET/CT扫描中计算HCC的最大标准化摄取值（SUVmax）。研究ALDOB表达与SUVmax之间的关系，并使用Cox比例风险模型和Kaplan-Meier生存分析评估它们对总生存期的影响。通过在HUH7和7721细胞中过表达ALDOB来分析其在肿瘤代谢中的作用。
根据TCGA数据库，与正常组织相比，HCC中ALDOB mRNA水平下调，且显著缩短了HCC患者的总生存期。在IHC结果中，HCC中ALDOB蛋白表达同样低于相邻正常组织（P<0.05），且与肿瘤大小（P<0.001）、高肿瘤-淋巴结-转移分期（P = 0.022）和升高的SUVmax（P = 0.009）显著相关。HCC中ALDOB表达与SUVmax呈负相关（r = -0.454；P = 0.012），预测其表达的最佳SUVmax临界值为4.15。在预后方面，低ALDOB表达或SUVmax≥3.9表明HCC患者总生存时间较短。此外，COX回归分析表明高SUVmax是HCC的独立预后危险因素（P = 0.036）。ALDOB表达阴性且SUVmax阳性（≥3.9）的HCC患者预后较差。HCC细胞中ALDOB过表达显著降低F-FDG摄取和乳酸生成。
HCC患者的SUVmax与ALDOB表达呈负相关，F-FDG PET/CT可能有助于预测ALDOB状态。联合使用ALDOB表达和F-FDG PET/CT数据可为HCC患者的疾病预后提供额外信息。
