Department of Gastrointestinal Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Medicine (Baltimore). 2022 Sep 9;101(36):e30219. doi: 10.1097/MD.0000000000030219.
Hepatocellular carcinoma (HCC) is the sixth most common cancer, which is characterized by complicated etiology, excessive heterogeneity, and poor prognosis. Necroptosis is a new kind of programmed cell death, which is intently associated with the occurrence and development of tumors. Although researchers have had a deep understanding of necroptosis in recent years, the expression level of necroptosis-related genes in HCC and its relationship with the survival time of HCC patients are not clear.
According to the expression of necroptosis-related genes and the survival of HCC patients, HCC patients in the TCGA database were divided into 2 groups that were relatively independent of each other. The genes related to the survival time of HCC patients were screened from the 2 groups of differentially expressed genes. By using the Least Absolute Shrinkage and Selection Operator Cox regression analysis, the optimal λ value was obtained, and the 10-gene signature model was established.
According to the median risk score of the TCGA cohort, HCC patients were averagely divided into high- and low-risk groups. Compared with the low-risk group, the death toll of the high-risk group was relatively higher and the survival time was relatively shorter. Principal component analysis and t-distributed stochastic neighbor embedding analysis showed that there was a significant separation between high- and low-risk groups. Through Kaplan-Meier analysis, it was found that the survival time of HCC patients in the high-risk group was significantly shorter than that in the low-risk group. Through receiver operating characteristic analysis, it was found that the sensitivity and specificity of the model were good. We also make a comprehensive analysis of the international cancer genome consortium database as a verification queue and prove the reliability of the 10-gene signature model. Gene Ontolog, Kyoto Encyclopedia of Genes and Genomes, and single-sample gene set enrichment analysis showed that many biological processes and pathways related to immunity had been enriched, and the antitumor immune function was weakened in the high-risk population.
The risk score can be considered as an independent prognostic factor to predict the prognosis of patients with HCC, and necroptosis-related genes are also closely related to tumor immune function.
肝细胞癌（HCC）是第六大常见癌症，其具有复杂的病因、高度异质性和预后不良的特点。细胞坏死性凋亡是一种新的程序性细胞死亡方式，与肿瘤的发生和发展密切相关。尽管近年来研究人员对细胞坏死性凋亡有了更深入的了解，但 HCC 中细胞坏死性凋亡相关基因的表达水平及其与 HCC 患者生存时间的关系尚不清楚。
根据 TCGA 数据库中 HCC 患者的细胞坏死性凋亡相关基因表达和生存情况，将患者分为两组，两组之间相对独立。从两组差异表达基因中筛选与 HCC 患者生存时间相关的基因。通过最小绝对收缩和选择算子 Cox 回归分析，得到最优 λ 值，并建立 10 基因特征模型。
根据 TCGA 队列的中位数风险评分，将 HCC 患者平均分为高低风险组。与低风险组相比，高风险组的死亡人数相对较高，生存时间相对较短。主成分分析和 t 分布随机邻域嵌入分析表明，高低风险组之间存在显著分离。通过 Kaplan-Meier 分析发现，高风险组 HCC 患者的生存时间明显短于低风险组。通过接受者操作特征分析发现，该模型的敏感性和特异性均较好。我们还对国际癌症基因组联盟数据库进行了综合分析作为验证队列，并证明了 10 基因特征模型的可靠性。基因本体论、京都基因与基因组百科全书和单样本基因集富集分析表明，许多与免疫相关的生物学过程和途径被富集，高风险人群的抗肿瘤免疫功能减弱。
风险评分可以被认为是一个独立的预后因素，可预测 HCC 患者的预后，细胞坏死性凋亡相关基因也与肿瘤免疫功能密切相关。
