Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Jiangxi Province Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Front Immunol. 2022 Sep 28;13:990790. doi: 10.3389/fimmu.2022.990790. eCollection 2022.
Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, with high incidence, high malignancy, and low survival rate. Cuproptosis is a novel form of cell death mediated by lipoylated TCA cycle proteins-mediated novel cell death pathway and is highly associated with mitochondrial metabolism. However, the relationship between the expression level of cuproptosis-related genes (CRGs) and the prognosis of HCC is still unclear.
Combining the HCC transcriptomic data from The Cancer Genome Atlas(TCGA) and Gene Expression Omnibus (GEO) databases, we identified the differentially expressed cuproptosis-related genes (DECRGs) and obtained the prognosis-related DECRGs through univariate regression analysis.LASSO and multivariate COX regression analyses of these DECRGs yielded four genes that were used to construct the signature. Next, we use ROC curves to evaluate the performance of signatures. The tumor microenvironment, immune infiltration, tumor mutation load, half-maximum suppression concentration, and immunotherapy effects were also compared between the low-risk and high-risk groups. Finally, we analyzed the expression level, prognosis, and immune infiltration correlation on the four genes that constructed the model.
Four DECRGs s were used to construct the signature. The ROC curves indicated that signature can better assess the prognosis of HCC patients. Patients were grouped according to the signature risk score. Patients in the low-risk group had a significantly longer survival time than those in the high-risk group. Furthermore, the tumor mutation burden (TMB) values were associated with the risk score and the higher-risk group had a higher proportion of TP53 mutations than the low-risk group.ESTIMATE analysis showed significant differences in stromal scores between the two groups.N6-methyladenosine (m6A) and multiple immune checkpoints were expressed at higher levels in the high-risk group. Then, we found that signature score correlated with chemotherapeutic drug sensitivity and immunotherapy efficacy in HCC patients. Finally, we further confirmed that the four DECRGs genes were associated with the prognosis of HCC through external validation.
We studied from the cuproptosis perspective and developed a new prognostic feature to predict the prognosis of HCC patients. This signature with good performance will help physicians to evaluate the overall prognosis of patients and may provide new ideas for clinical decision-making and treatment strategies.
肝细胞癌（HCC）是世界上最常见的恶性肿瘤之一，具有发病率高、恶性程度高、生存率低的特点。铜死亡是一种新型的细胞死亡形式，由脂酰化 TCA 循环蛋白介导的新型细胞死亡途径介导，与线粒体代谢高度相关。然而，铜死亡相关基因（CRG）的表达水平与 HCC 预后之间的关系尚不清楚。
结合癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）中的 HCC 转录组数据，我们鉴定了差异表达的铜死亡相关基因（DECRG），并通过单因素回归分析获得了与预后相关的 DECRG。LASSO 和多变量 COX 回归分析这些 DECRG 得到了 4 个基因，用于构建特征。接下来，我们使用 ROC 曲线评估特征的性能。还比较了低风险组和高风险组之间的肿瘤微环境、免疫浸润、肿瘤突变负荷、半抑制浓度和免疫治疗效果。最后，我们分析了模型中构建的四个基因的表达水平、预后和免疫浸润相关性。
我们使用 4 个 DECRG 构建了特征。ROC 曲线表明，该特征能更好地评估 HCC 患者的预后。根据特征风险评分将患者分组。低风险组患者的生存时间明显长于高风险组患者。此外，肿瘤突变负荷（TMB）值与风险评分相关，高风险组中 TP53 突变的比例高于低风险组。ESTIMATE 分析显示两组间基质评分差异显著。高风险组中 N6-甲基腺苷（m6A）和多个免疫检查点的表达水平较高。然后，我们发现特征评分与 HCC 患者的化疗药物敏感性和免疫治疗疗效相关。最后，我们通过外部验证进一步证实了四个 DECRG 基因与 HCC 的预后相关。
我们从铜死亡的角度进行研究，开发了一种新的预后特征来预测 HCC 患者的预后。该特征具有良好的性能，将有助于医生评估患者的总体预后，并可能为临床决策和治疗策略提供新的思路。
Zotero 插件
