AUTHOR=Jia Wenzhi , Wu Qianyun , Yu Xiaofeng , Shen Mengqin , Zhang Ruixue , Li Jiajin , Zhao Li , Huang Gang , Liu Jianjun 

TITLE=Prognostic values of ALDOB expression and 18F-FDG PET/CT in hepatocellular carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.1044902

DOI=10.3389/fonc.2022.1044902

ISSN=2234-943X

ABSTRACT=Purpose
The glycolytic enzyme fructose 1,6-bisphosphate aldolase B (ALDOB) is aberrantly expressed and impacts the prognosis in HCC. Hepatic ALDOB loss leads to paradoxical upregulation of glucose metabolism, favoring hepatocellular carcinogenesis. Nevertheless, the relationship between ALDOB expression and 18F-FDG uptake, and their effects on HCC prognosis remain unclear. We evaluated whether ALDOB expression is associated with 18F-FDG uptake and their impact on HCC prognosis prediction.
Methods
Changes in ALDOB expression levels and the prognostic values in HCC were analyzed using data from The Cancer Genome Atlas database. Ultimately, 34 patients with HCC who underwent 18F-FDG PET/CT preoperatively were enrolled in this retrospective study. ALDOB expression was determined using immunohistochemistry staining, and SUVmax of HCC was calculated from the 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.
Results
According to TCGA database, the ALDOB mRNA level was widely downregulated between matched tumor and normal samples in different cancer types, including HCC, 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 18F-FDG uptake and lactate production.
Conclusion
SUVmax in HCC patients is inversely correlated with ALDOB expression, and PET/CT may be useful for ALDOB status prediction. The combined use of ALDOB expression and PET/CT data can provide additional information on disease prognosis in HCC patients.