Wang Gongjun, Ding Baoning, Sun Libin, Guo Jing, Wang Shasha, Li Wenqian, Zhang Yuqi, Lv Jing, Qiu Wensheng
Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, China.
School of Statistics, Shandong University of Finance and Economics, Jinan, China.
Front Genet. 2022 Apr 11;13:859544. doi: 10.3389/fgene.2022.859544. eCollection 2022.
Liver hepatocellular carcinoma (LIHC) is a widespread and often deadly neoplasm. There is increasing evidence that necroptosis mediates numerous tumor-associated behaviors, as well as the regulation of the tumor microenvironment, suggesting its use as a biomarker for tumor prognosis. Data on mRNA expression and necroptosis regulators were acquired from the TCGA and KEGG databases, respectively. Clinical liver hepatocellular carcinoma (LIHC) patient data and information on the expression of necroptosis regulators were processed by unsupervised cluster analysis was performed on LIHC patients together with necroptotic regulator expression and, differentially expressed necroptosis-related genes (DENRGs) were identified by comparing the two clusters. A signature based on eight DENRGs was constructed and verified through independent data sets, and its relationship with the tumor microenvironment was investigated. Unsupervised cluster analysis demonstrated inherent immune differences among LIHC patients. In all, 1,516 DENRGs were obtained by comparison between the two clusters. In the training set, the final eight genes obtained by univariate, LASSO, and multivariate Cox regression were utilized for constructing the signature. The survival and receiver operating characteristic (ROC) curve achieved satisfactory results in both sets. The high-risk group was characterized by greater immune infiltration and poor prognosis. The results of survival analysis based on the expression of eight DENRGs further confirmed the signature. We established and validated a risk signature based on eight DERNGs related to the tumor microenvironment. This provides a possible explanation for the different clinical effects of immunotherapy and provides a novel perspective for predicting tumor prognosis in LIHC.
肝细胞癌（LIHC）是一种广泛存在且往往致命的肿瘤。越来越多的证据表明，坏死性凋亡介导了许多肿瘤相关行为以及肿瘤微环境的调节，这表明其可作为肿瘤预后的生物标志物。分别从TCGA和KEGG数据库获取mRNA表达和坏死性凋亡调节因子的数据。对临床肝细胞癌（LIHC）患者数据以及坏死性凋亡调节因子的表达信息进行处理，通过无监督聚类分析对LIHC患者与坏死性凋亡调节因子表达进行分析，并通过比较两个聚类来鉴定差异表达的坏死性凋亡相关基因（DENRGs）。构建了一个基于八个DENRGs的特征，并通过独立数据集进行验证，同时研究了其与肿瘤微环境的关系。无监督聚类分析显示LIHC患者之间存在内在的免疫差异。总共通过比较两个聚类获得了1516个DENRGs。在训练集中，通过单变量、LASSO和多变量Cox回归最终获得的八个基因用于构建特征。生存曲线和受试者工作特征（ROC）曲线在两个数据集中均取得了令人满意的结果。高风险组的特征是免疫浸润程度更高且预后较差。基于八个DENRGs表达的生存分析结果进一步证实了该特征。我们建立并验证了一个基于与肿瘤微环境相关的八个DERNGs的风险特征。这为免疫治疗的不同临床效果提供了一种可能的解释，并为预测LIHC患者的肿瘤预后提供了新的视角。
