Ma Hui, Yu Ting, Li Zhong-Chen, Zhang Lan, Chen Rong-Xin, Ren Zheng-Gang
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Department of Hepatic Oncology, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, People's Republic of China.
J Hepatocell Carcinoma. 2024 Aug 13;11:1569-1580. doi: 10.2147/JHC.S465592. eCollection 2024.
Oxidative stress plays a critical role in promoting tumor resistance to hypoxia and chemotherapeutic drugs. However, the prognostic role of oxidative stress-related genes (OSRGs) in hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) has not been fully explored.
We used transcriptome data from the GSE104580 cohort containing patients marked as responders or nonresponders to TACE therapy to identify differentially expressed OSRGs associated with TACE response (TR-OSRGs). We created a TR-OSRG prognostic signature based on TR-OSRGs using least absolute shrinkage and selection operator Cox and stepwise Cox regression analyses in a training cohort of patients with HCC (TCGA-LIHC). We verified this prognostic signature in two external cohorts of patients who received TACE for HCC (GSE14520-TACE and ZS-TACE-37). Finally, we constructed a prognostic nomogram model for predicting survival probability of patients with HCC based on Cox regression analysis.
The TR-OSRG prognostic signature was created and shown to be a robust independent prognostic factor for treatment response and outcomes for HCC after TACE therapy. Risk scores based on this signature correlated with tumor stage and grade. Tumor samples from patients with higher risk scores exhibited more infiltration of immune cells and significantly increased expression of immune checkpoint genes. We also developed a nomogram for patients with HCC based on the TR-OSRG prognostic signature and clinical parameters; this nomogram was a useful quantitative analysis tool for predicting patient survival.
The TR-OSRGs signature exhibited good performance in predicting treatment response and outcomes in patients with HCC treated with TACE.
氧化应激在促进肿瘤对缺氧和化疗药物的耐药性方面起着关键作用。然而，氧化应激相关基因（OSRGs）在经动脉化疗栓塞（TACE）治疗的肝细胞癌（HCC）中的预后作用尚未得到充分研究。
我们使用了来自GSE104580队列的转录组数据，该队列包含标记为TACE治疗反应者或无反应者的患者，以识别与TACE反应相关的差异表达OSRGs（TR-OSRGs）。我们在HCC患者（TCGA-LIHC）的训练队列中，使用最小绝对收缩和选择算子Cox回归分析以及逐步Cox回归分析，基于TR-OSRGs创建了一个TR-OSRG预后特征。我们在两个接受HCC TACE治疗的患者外部队列（GSE14520-TACE和ZS-TACE-37）中验证了这一预后特征。最后，我们基于Cox回归分析构建了一个预测HCC患者生存概率的预后列线图模型。
创建了TR-OSRG预后特征，并显示其是TACE治疗后HCC治疗反应和结局的强大独立预后因素。基于该特征的风险评分与肿瘤分期和分级相关。风险评分较高患者的肿瘤样本表现出更多免疫细胞浸润，免疫检查点基因表达显著增加。我们还基于TR-OSRG预后特征和临床参数为HCC患者开发了一个列线图；该列线图是预测患者生存的有用定量分析工具。
TR-OSRGs特征在预测接受TACE治疗的HCC患者的治疗反应和结局方面表现良好。
