肝细胞癌中与二硫化物驱动细胞死亡和免疫浸润相关的预后风险模型的建立。
Establishment of prognostic risk model related to disulfidptosis and immune infiltration in hepatocellular carcinoma.
作者信息
Xu Zhe, Pang Chong, Xu Xundi
机构信息
Department of Breast and Thyroid Surgery, South China Hospital, Medical School, Shenzhen University, Shenzhen, 518116, PR China.
Department of Hepatobiliary Pancreatic Surgery, South China Hospital, Medical School, Shenzhen University, Shenzhen, 518116, PR China.
出版信息
Heliyon. 2024 Nov 14;10(23):e40405. doi: 10.1016/j.heliyon.2024.e40405. eCollection 2024 Dec 15.
BACKGROUND
Disulfidptosis is a newly discovered type of cell death. We aim to identify hub genes associated with both disulfidptosis and immune infiltration in hepatocellular carcinoma (HCC) patients, and to develop an individualized risk prediction model.
METHODS
The TCGA-LIHC cohort was utilized as the training set to identify molecular subtypes associated with disulfidptosis and to perform immune infiltration analysis. WGCNA, univariate Cox, and LASSO algorithm were employed to select hub genes for constructing the prognostic model. ICGC-LIRI cohort was utilized as an independent testing set. Validation of the expression of hub genes was performed using qRT-PCR and Western blot.
RESULTS
Cluster 1 was identified as the disulfidptosis associated molecular subtype, characterized by higher expression of disulfidptosis related genes (DRGs) and immune infiltration levels. ANXA2, MSC, and ST6GALNAC4 were identified as hub genes for calculating the risk score. The high-risk group were more likely to benefit from immunotherapy, targeted therapy and chemotherapy. A prognostic model was developed combining clinicopathological factors with satisfactory predictive accuracy. The hub genes were found upregulated in HCC cell line.
CONCLUSIONS
Our findings provide valuable theoretical support for prognostic prediction and the evaluation of therapeutic outcomes in relation to disulfidptosis and immune infiltration in HCC, highlighting the importance of conducting in-depth research on disulfidptosis-related mechanisms.
背景
二硫化物诱导的细胞死亡是一种新发现的细胞死亡类型。我们旨在鉴定与肝细胞癌（HCC）患者的二硫化物诱导的细胞死亡和免疫浸润相关的枢纽基因，并建立个性化风险预测模型。
方法
将TCGA-LIHC队列用作训练集，以鉴定与二硫化物诱导的细胞死亡相关的分子亚型并进行免疫浸润分析。采用加权基因共表达网络分析（WGCNA）、单变量Cox分析和套索（LASSO）算法选择枢纽基因来构建预后模型。将ICGC-LIRI队列用作独立测试集。使用qRT-PCR和蛋白质免疫印迹法对枢纽基因的表达进行验证。
结果
聚类1被鉴定为与二硫化物诱导的细胞死亡相关的分子亚型，其特征是二硫化物诱导的细胞死亡相关基因（DRGs）表达较高且免疫浸润水平较高。鉴定出膜联蛋白A2（ANXA2）、间充质干细胞（MSC）和N-乙酰神经氨酸α-2,6-唾液酸转移酶4（ST6GALNAC4）作为计算风险评分的枢纽基因。高危组更有可能从免疫治疗、靶向治疗和化疗中获益。结合临床病理因素建立了一个预后模型，其预测准确性令人满意。发现枢纽基因在肝癌细胞系中上调。
结论
我们的研究结果为HCC中与二硫化物诱导的细胞死亡和免疫浸润相关的预后预测及治疗效果评估提供了有价值的理论支持，突出了对二硫化物诱导的细胞死亡相关机制进行深入研究的重要性。
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