Song Shu-Shu, Ying Jia-Fu, Zhang You-Ni, Pan Hong-Ying, He Xiang-Lei, Hu Zhi-Ming, Wang Hui-Ju, Dou Xiao-Bing, Mou Xiao-Zhou
College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China.
Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang 310014, P.R. China.
Oncol Lett. 2020 Apr;19(4):3181-3188. doi: 10.3892/ol.2020.11430. Epub 2020 Mar 3.
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 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.
叉头框O3(FOXO3)作为一种肿瘤抑制基因的作用及其与人类寿命的关联已有充分记载。然而,多项研究表明,FOXO3的高表达也与肿瘤发生显著相关。本研究的目的是确定FOXO3在肝细胞癌(HCC)发生发展及预后中的临床意义。通过UALCAN在线工具分析来自癌症基因组图谱数据库的FOXO3的mRNA表达数据,以比较HCC与正常肝组织中FOXO3的表达。随后,通过对314例HCC和150例非癌肝组织样本进行免疫组织化学染色,研究FOXO3在蛋白水平的表达。使用χ检验分析蛋白表达与临床病理参数之间的关联,并通过Kaplan-Meier分析评估FOXO3表达对生存的影响。与健康组织相比,HCC中FOXO3 mRNA的表达显著更高。在150例非癌肝组织中有43例显示FOXO3蛋白高表达,在314例HCC样本中有238例。FOXO3表达与转移、肿瘤-淋巴结-转移分期、Edmondson分级、甲胎蛋白水平及总生存期之间存在显著关联。总之,FOXO3的高表达预示着HCC患者预后不良,表明该蛋白是HCC潜在的治疗靶点。