the role of forkhead box O3 (FOXO3) as a tumor suppressor gene and its association with the human lifespan is well documented. However, several studies have indicated that high expression of FOXO3 is also significantly associated with tumorigenesis. the aim of the present study was to determine the clinical significance of FOXO3 in the development and prognosis of hepatocellular carcinoma (Hcc). mrnA expression data of FOXO3 from the cancer genome Atlas database was analyzed through the UAlcAn online tool to compare the expression of FOXO3 between Hcc and normal liver tissues. subsequently, the expression of FOXO3 at the protein level was investigated via immunohistochemical staining of 314 Hcc and 150 non-cancerous liver tissue samples. the association between protein expression and clinicopathological parameters was analyzed using the χ 2 test, and the effect of FOXO3 expression on survival was assessed via Kaplan-Meier analysis. the expression of FOXO3 mRNA was significantly higher in HCC in comparison with healthy tissues. High FOXO3 protein expression was revealed in 43/150 non-cancerous liver tissues, and in 238/314 Hcc samples. A significant association was demonstrated between FOXO3 expression and metastasis, tumor-node-Metastasis stage, edmondson grade, α-fetoprotein level and overall survival. In conclusion, the high expression of FOXO3 predicts a poor prognosis in patients with Hcc, indicating this protein as a potential therapeutic target in Hcc.

Beta-glucosidase (GBA), also known as acid β-glucosidase, exhibits an activity of glucosylceramidase (EC 3.2.1.45). Three main isoforms of β-glucosidases have been identified in mammals: GBA1, GBA2, and GBA3. The deficiency of these enzymes leads to glucosylceramide accumulation, resulting in Gaucher's disease. The present study is focused on the cytosolic β-glucosidase, GBA3, and its relationship with hepatocellular carcinoma (HCC). The expression of GBA3 mRNA in HCC was evaluated first using the TCGA database, and then by immunohistochemistry using tissue microarrays of 328 clinically characterized HCC samples and 151 non-tumor liver controls. Moreover, the presence of a correlation between GBA3 expression and clinicopathological characteristics of patients was examined. The obtained results indicated that the expression of GBA3 mRNA was significantly lower in HCC than in the adjacent non-tumor liver tissues. The expression of GBA3 was inversely related to the number of tumors (p=0.041), tumor size (p<0.001), Edmondson grade (p=0.007), microvascular invasion (p=0.049), patient status (p<0.001), and α-fetoprotein level (p<0.001). Patients exhibiting low GBA3 expression had a shorter survival time than those with high expression (p<0.001). In conclusion, the decreased GBA3 expression is strongly associated with a poor prognosis in HCC patients, and GBA3 may be a potential therapeutic target for HCC.