Yin Chang-Qing, Song Chun-Qing
College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310024, China.
Cells. 2024 Dec 19;13(24):2102. doi: 10.3390/cells13242102.
Hepatocellular carcinoma (HCC) is clinically distinguished by its covert onset, rapid progression, high recurrence rate, and poor prognosis. Studies have revealed that SETDB1 (SET Domain Bifurcated 1) is a histone H3 methyltransferase located on chromosome 1 and plays a crucial role in carcinogenesis. Therefore, we aimed to evaluate the clinical significance of SETDB1 expression in HCC. In patients with HCC, elevated levels of SETDB1 correlated with a poorer overall survival (OS) rate, marking it as an independent prognostic factor for HCC, as revealed by both univariate and multivariate Cox analyses. Furthermore, we utilized the SangerBox and TISIDB databases to profile the tumor immune microenvironment in HCC, including scoring the tumor microenvironment and assessing immune cell infiltration. The TIDE algorithm was employed to examine the association between SETDB1 expression and immune responses. Our findings indicated that SETDB1 expression negatively correlated with the majority of immune cells, a wide range of immune cell marker genes, and numerous immune pathways, thereby leading to the reduced effectiveness of immune checkpoint inhibitors. Lastly, both in vivo and ex vivo experiments were conducted to substantiate the role of SETDB1 in HCC tumorigenesis. In conclusion, the upregulation of SETDB1 is associated with a poorer prognosis in HCC patients and inversely correlates with immune cell infiltration, potentially serving as a predictive marker for immunotherapy response.
肝细胞癌（HCC）在临床上的特点是起病隐匿、进展迅速、复发率高且预后较差。研究表明，SETDB1（SET结构域分叉1）是一种位于1号染色体上的组蛋白H3甲基转移酶，在肿瘤发生过程中起关键作用。因此，我们旨在评估SETDB1表达在HCC中的临床意义。单因素和多因素Cox分析均显示，在HCC患者中，SETDB1水平升高与较差的总生存率（OS）相关，这表明它是HCC的一个独立预后因素。此外，我们利用SangerBox和TISIDB数据库对HCC中的肿瘤免疫微环境进行分析，包括对肿瘤微环境进行评分和评估免疫细胞浸润情况。采用TIDE算法研究SETDB1表达与免疫反应之间的关联。我们的研究结果表明，SETDB1表达与大多数免疫细胞、多种免疫细胞标记基因以及众多免疫途径呈负相关，从而导致免疫检查点抑制剂的疗效降低。最后，进行了体内和体外实验以证实SETDB1在HCC肿瘤发生中的作用。总之，SETDB1的上调与HCC患者较差的预后相关，并且与免疫细胞浸润呈负相关，可能作为免疫治疗反应的预测标志物。
