Wang Xilong, Xiao Ke, Liu Zhipu, Wang Li, Dong Zhaogang, Wang Hongxing, Wang Yuhui
Department of Clinical Laboratory, Weifang People's Hospital, Weifang, 261000, China.
Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, 250012, China.
J Cancer. 2024 Aug 26;15(17):5540-5556. doi: 10.7150/jca.93194. eCollection 2024.
Disulfidptosis, a recently unveiled mechanism of demise, has been linked to an unfavorable prognosis in the context of hepatocellular carcinoma (HCC). However, few studies have focused on the causal link between disulfidptosis and HBV-related HCC (HBV-HCC). In this study, the Mendelian randomization (MR) analysis demonstrated that the risk of HCC increased with increasing genetic susceptibility to HBV, and the genetic changes of disulfidptosis were significantly associated with the increased risk of HBV-HCC. Within both the TCGA and GEO cohorts, it is possible to accurately forecast the prognosis of HBV-HCC by utilizing a risk score that is derived from a combination of GYS1, RPN1, SLC7A11, LRPPRC and CAPZB genes. GYS1, a potential therapeutic target for HBV-HCC, exhibits a remarkable positive correlation with immune infiltration and MSI when compared to other molecules. Furthermore, we demonstrated that silencing GYS1 effectively inhibits the tumor proliferation and metastasis of HBV-HCC . Overall, this study expands the understanding of the potential roles of disulfidptosis in HBV-HCC and highlights GYS1 as a promising target for HBV-HCC.
二硫化物诱导的细胞死亡是一种最近才被揭示的细胞死亡机制，在肝细胞癌（HCC）的背景下与不良预后相关。然而，很少有研究关注二硫化物诱导的细胞死亡与乙型肝炎病毒相关肝细胞癌（HBV-HCC）之间的因果关系。在本研究中，孟德尔随机化（MR）分析表明，HCC的风险随着对HBV遗传易感性的增加而增加，并且二硫化物诱导的细胞死亡的基因变化与HBV-HCC风险增加显著相关。在TCGA和GEO队列中，利用由GYS1、RPN1、SLC7A11、LRPPRC和CAPZB基因组合得出的风险评分，可以准确预测HBV-HCC的预后。与其他分子相比，GYS1作为HBV-HCC的潜在治疗靶点，与免疫浸润和微卫星不稳定性（MSI）呈现出显著的正相关。此外，我们证明沉默GYS1可有效抑制HBV-HCC的肿瘤增殖和转移。总体而言，本研究扩展了对二硫化物诱导的细胞死亡在HBV-HCC中潜在作用的理解，并突出了GYS1作为HBV-HCC有前景的治疗靶点。
