肝细胞癌是世界范围内广泛传播的癌症，是第五大常见癌症和第四大癌症相关死亡原因。综合研究发现，磷酸化激酶TLK2在促进肿瘤发生发展中发挥着至关重要的作用。然而，TLK2对肝细胞癌肿瘤细胞和免疫微环境的预后意义和影响仍有待探索，值得进一步研究。本研究的目的是探讨TLK2在促进肝细胞癌发生发展中的作用。本研究利用癌症基因组图谱(TCGA)数据库和其他数据库作为训练集来检测TLK2的表达及其预后意义。随后通过细胞增殖测定和细胞集落测定验证了这些发现。采用基因集富集分析（GSEA）研究肝细胞癌中与TLK2相关的肿瘤相关生物学过程，同时通过TCGA数据集分析TLK2表达与Wnt/β-catenin信号通路之间的关系。 Western blotting和免疫荧光检测证实了实验结果。TLK2在肿瘤组织中的表达水平高于正常组织。甲胎蛋白(AFP)、T分期、病理分期和组织学分级与TLK2表达显着相关。 TLK2 高表达与较差的总生存期 (OS) [风险比 (HR) =1.62，95% 置信区间 (CI)：1.14-2.29，P=0.007]、无进展生存期 (PFS) (HR =1.88, 95) 相关训练和验证集中的 % CI：1.40-2.52，P<0.001）和疾病特异性生存 (DSS)（HR = 1.86，95% CI：1.18-2.93，P=0.007）。单变量和多变量分析均表明 TLK2 是一个独立的预后因素。 GSEA显示TLK2在肿瘤相关的生物过程中显着富集。 TLK2 诱导 β-连环蛋白信号的激活，导致肿瘤持续生长。甲基噻唑基四唑 (MTT) 和集落形成试验表明 TLK2 可以促进肝细胞癌进展。此外，TLK2 显示与 Wnt 通路中的 β-catenin 显着相关。TLK2 代表肝细胞癌的独立预后因素，可通过 β-catenin 信号通路促进癌症进展。2024 转化癌症研究。版权所有。

Hepatocellular carcinoma is a widespread cancer worldwide, ranking as the fifth most frequent cancer and the fourth leading cause of cancer-related deaths. According to comprehensive research, TLK2, a phosphorylated kinase, has been discovered to play a crucial role in promoting tumor development. However, the prognostic significance and influence of TLK2 on hepatocellular carcinoma tumor cells and the immune microenvironment remain unexplored, warranting further investigation. The aim of this study was to investigate the role of TLK2 in promoting the development of hepatocellular carcinoma.The present study utilized The Cancer Genome Atlas (TCGA) database and other databases as training sets to examine the expression of TLK2 and its prognostic significance. The findings were subsequently validated through cell proliferation assays and cell colony assays. Gene set enrichment analysis (GSEA) was employed to investigate the tumor-related biological processes associated with TLK2 in hepatocellular carcinoma, while the relationship between TLK2 expression and Wnt/β-catenin signaling pathway was analyzed via TCGA dataset analysis. Western blotting and immunofluorescence assays were used to confirm the experimental results.TLK2 showed higher expression levels in tumor tissues than in normal tissues. Alpha fetoprotein (AFP), T stage, pathological stage, and histological grade were significantly associated with TLK2 expression. High TLK2 expression correlated with worse overall survival (OS) [hazard ratio (HR) =1.62, 95% confidence interval (CI): 1.14-2.29, P=0.007], progression-free survival (PFS) (HR =1.88, 95% CI: 1.40-2.52, P<0.001) and disease specific survival (DSS) (HR =1.86, 95% CI: 1.18-2.93, P=0.007) in the training and validation sets. Both univariate and multivariate analyses showed that TLK2 was an independent prognostic factor. GSEA showed that TLK2 was significantly enriched in tumor-related biological processes. TLK2 induced the activation of β-catenin signaling, resulting in sustained tumor growth. Methyl thiazolyl tetrazolium (MTT) and colony formation assays demonstrated that TLK2 could promote hepatocellular carcinoma progression. Furthermore, TLK2 showed a significant association with β-catenin in the Wnt pathway.TLK2 represents an independent prognostic factor in hepatocellular carcinoma and can promote cancer progression via the β-catenin signaling pathway.2024 Translational Cancer Research. All rights reserved.