Peng YunZhen, Wu GuoJing, Qiu Xin, Luo Yue, Zou YiShu, Wei XueYan, Li Aimin
Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
Department of Urology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.
Front Genet. 2022 Aug 30;13:916024. doi: 10.3389/fgene.2022.916024. eCollection 2022.
Immunotherapy has achieved remarkable success in treating advanced liver cancer. Current evidence shows that most of the available immune checkpoint inhibitor (ICB) treatments are suboptimal, and specific markers are needed for patients regarded as good candidates for immunotherapy. Necroptosis, a type of programmed cell death, plays an important role in hepatocellular carcinoma (HCC) progression and outcome. However, studies on the necroptosis-related lncRNA in HCC are scarce. In this view, the present study investigates the link among necroptosis-related lncRNA, prognosis, immune microenvironment, and immunotherapy response. Gene transcriptome and clinical data were retrieved from The Genome Atlas database. Pearson correlation analysis of necroptosis-related genes was performed to identify necroptosis-related lncRNAs. The Wilcoxon method was used to detect differentially expressed genes, and prognostic relevant lncRNAs were obtained by univariate Cox regression analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were utilized to perform functional enrichment analysis. Lasso-Cox stepwise regression analysis was employed to calculate risk score, which was involved in analyzing immune cells infiltration, immune checkpoints expression, and predicting immunotherapeutic efficacy. Quantitative RT-PCR (qRT-PCR) was performed to detect the expression pattern of lncRNA in cell lines. The 10 lncRNAs generated in this study were used to create a prognostic risk model for HCC and group patients into groups based on risk. High-risk patients with HCC have a significantly lower OS rate than low-risk patients. Multivariate Cox regression analysis showed that risk score is an independent risk factor for HCC with high accuracy. Patients in the high-risk group exhibited a weaker immune surveillance and higher expression level of immune checkpoint molecules. In terms of drug resistance, patients in the low-risk group were more sensitive to sorafenib. The OS-related nomogram was constructed to verify the accuracy of our model. Finally, quantitative RT-PCR experiments were used to verify the expression patterns of candidate genes. The lncRNA signature established herein, encompassing 10 necroptosis-related lncRNAs, is valuable for survival prediction and holds promise as prognostic markers for HCC.
免疫疗法在治疗晚期肝癌方面取得了显著成功。目前的证据表明，大多数现有的免疫检查点抑制剂（ICB）治疗效果欠佳，对于被视为免疫疗法良好候选者的患者需要特定的标志物。坏死性凋亡是一种程序性细胞死亡，在肝细胞癌（HCC）的进展和转归中起重要作用。然而，关于HCC中与坏死性凋亡相关的长链非编码RNA（lncRNA）的研究很少。有鉴于此，本研究探讨了与坏死性凋亡相关的lncRNA、预后、免疫微环境和免疫治疗反应之间的联系。从基因组图谱数据库中检索基因转录组和临床数据。对与坏死性凋亡相关的基因进行Pearson相关性分析，以鉴定与坏死性凋亡相关的lncRNA。采用Wilcoxon方法检测差异表达基因，并通过单因素Cox回归分析获得与预后相关的lncRNA。利用基因本体论和京都基因与基因组百科全书分析进行功能富集分析。采用Lasso-Cox逐步回归分析计算风险评分，该评分用于分析免疫细胞浸润、免疫检查点表达，并预测免疫治疗疗效。进行定量逆转录聚合酶链反应（qRT-PCR）以检测细胞系中lncRNA的表达模式。本研究中产生的10种lncRNA用于建立HCC的预后风险模型，并根据风险将患者分组。HCC高危患者的总生存率明显低于低危患者。多因素Cox回归分析表明，风险评分是HCC的独立危险因素，准确性高。高危组患者表现出较弱的免疫监视和较高的免疫检查点分子表达水平。在耐药性方面，低危组患者对索拉非尼更敏感。构建了与总生存相关的列线图以验证我们模型的准确性。最后，通过qRT-PCR实验验证候选基因的表达模式。本文建立的lncRNA特征，包含10种与坏死性凋亡相关的lncRNA，对生存预测有价值，有望成为HCC的预后标志物。
