Guan Songmei, Lin Qiang, Huang Peiwu, Lin Kangqiang, Duan Shigang
Department of Clinical Pharmacy, Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangzhou 524003, P.R. China.
Department of Hepatobiliary Surgery, Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangzhou 524003, P.R. China.
Oncol Lett. 2025 Mar 13;29(5):230. doi: 10.3892/ol.2025.14976. eCollection 2025 May.
Although numerous molecular classifications are available to predict the prognosis of patients with hepatocellular carcinoma (HCC), they are still unsatisfactory. Forkhead box O3 (FOXO3) has been widely reported as a transcription factor involved in human cancers, but its role in HCC remains controversial. The present study aimed to explore the role of FOXO3 in HCC, as well as to identify biomarkers and construct prognostic models based on FOXO3. FOXO3 was highly expressed in HCC and was closely associated with poor prognosis in The Cancer Genome Atlas (the training set) and International Cancer Genome Consortium (the validation set). Subsequently, a co-expression network indicated that the red modules were closely related to FOXO3. Five key FOXO3-related genes [DEAD-box helicase 55 (DDX55), RAB10, member RAS oncogene family (RAB10), RAB7A, TATA-box binding protein associated factor, RNA polymerase I subunit B (TAF1B) and TAF3] were obtained using Cox-least absolute shrinkage and selection operator analyses. The 5-gene signature successfully predicted the prognosis of patients with HCC in both the training and validation sets. Enrichment analysis suggested marked differences in AKT and cell cycle-related (E2F targets and G/M checkpoints) pathways between HCC subgroups. Furthermore, the tumor microenvironment analysis suggested that the difference in the distribution of M2 macrophages among various subgroups may contribute to the poor prognosis using the CIBERSORTx framework. Furthermore, the mRNA and protein expressions of DDX55, RAB10, RAB7A, TAF1B and TAF3 were found to be higher in HCC tissues compared with paracancerous tissues using RT-qPCR and western blotting. Additionally, knockdown of RAB10, RAB7A and TAF3 inhibited proliferation of Huh7 cells, assessed by a Cell Counting Kit-8 assay. In conclusion, a novel FOXO3-related model was constructed and revealed that RAB10, RAB7A and TAF3 may be potential molecular targets or biomarkers for HCC.
尽管有多种分子分类方法可用于预测肝细胞癌（HCC）患者的预后，但它们仍不尽人意。叉头框O3（FOXO3）作为一种参与人类癌症的转录因子已被广泛报道，但其在HCC中的作用仍存在争议。本研究旨在探讨FOXO3在HCC中的作用，并基于FOXO3鉴定生物标志物并构建预后模型。FOXO3在HCC中高表达，并且在癌症基因组图谱（训练集）和国际癌症基因组联盟（验证集）中与不良预后密切相关。随后，一个共表达网络表明红色模块与FOXO3密切相关。使用Cox最小绝对收缩和选择算子分析获得了五个关键的FOXO3相关基因[DEAD盒解旋酶55（DDX55）、RAB10，RAS癌基因家族成员（RAB10）、RAB7A、TATA盒结合蛋白相关因子、RNA聚合酶I亚基B（TAF1B）和TAF3]。这5个基因特征在训练集和验证集中均成功预测了HCC患者的预后。富集分析表明HCC亚组之间在AKT和细胞周期相关（E2F靶点和G/M检查点）途径上存在显著差异。此外，肿瘤微环境分析表明，使用CIBERSORTx框架，不同亚组之间M2巨噬细胞分布的差异可能导致预后不良。此外，使用RT-qPCR和蛋白质免疫印迹法发现，与癌旁组织相比，HCC组织中DDX55、RAB10、RAB7A、TAF1B和TAF3的mRNA和蛋白质表达更高。此外，通过细胞计数试剂盒-8检测评估，敲低RAB10、RAB7A和TAF3可抑制Huh7细胞的增殖。总之，构建了一种新型的FOXO3相关模型，揭示RAB10、RAB7A和TAF3可能是HCC潜在的分子靶点或生物标志物。
