School of Medicine, Guangxi University, Nanning, China.
Guangxi Scientific Research Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, China.
Front Immunol. 2023 Mar 30;14:1146411. doi: 10.3389/fimmu.2023.1146411. eCollection 2023.
Hepatocellular carcinoma is the third most deadly malignant tumor in the world with a poor prognosis. Although immunotherapy represents a promising therapeutic approach for HCC, the overall response rate of HCC patients to immunotherapy is less than 30%. Therefore, it is of great significance to explore prognostic factors and investigate the associated tumor immune microenvironment features.
By analyzing RNA-seq data of the TCGA-LIHC cohort, the set of cuproptosis related genes was extracted correlation analysis as a generalization feature. Then, a random forest cox prognostic model was constructed and the cuproptosis random forest cox score was built by random forest feature filtering and univariate multivariate cox regression analysis. Subsequently, the prognosis prediction of CRFCS was evaluated analyzing data of independent cohorts from GEO and ICGC by using KM and ROC methods. Moreover, mutation characterization, immune cell infiltration, immune evasion, and drug sensitivity of CRFCS in HCC were assessed.
A cuproptosis random forest cox score was built based on a generalization feature of four cuproptosis related genes. Patients in the high CRFCS group exhibited a lower overall survival. Univariate multivariate Cox regression analysis validated CRFCS as an independent prognostic indicator. ROC analysis revealed that CRFCS was a good predictor of HCC (AUC =0.82). Mutation analysis manifested that microsatellite instability (MSI) was significantly increased in the high CRFCS group. Meanwhile, tumor microenvironment analysis showed that the high CRFCS group displayed much more immune cell infiltration compared with the low CRFCS group. The immune escape assessment analysis demonstrated that the high CRFCS group displayed a decreased TIDE score indicating a lower immune escape probability in the high CRFCS group compared with the low CRFCS group. Interestingly, immune checkpoints were highly expressed in the high CRFCS group. Drug sensitivity analysis revealed that HCC patients from the high CRFCS group had a lower IC of sorafenib than that from the low CRFCS group.
In this study, we constructed a cuproptosis random forest cox score (CRFCS) model. CRFCS was revealed to be a potential independent prognostic indicator of HCC and high CRFCS samples showed a poor prognosis. Interestingly, CRFCS were correlated with TME characteristics as well as clinical treatment efficacy. Importantly, compared with the low CRFCS group, the high CRFCS group may benefit from immunotherapy and sorafenib treatment.
肝细胞癌是世界上第三致命的恶性肿瘤，预后不良。尽管免疫疗法是 HCC 的一种很有前途的治疗方法，但 HCC 患者对免疫疗法的总体反应率低于 30%。因此，探索预后因素并研究相关肿瘤免疫微环境特征具有重要意义。
通过分析 TCGA-LIHC 队列的 RNA-seq 数据，提取了一组铜死亡相关基因作为泛化特征。然后，构建了一个随机森林 Cox 预后模型，并通过随机森林特征筛选和单变量多变量 Cox 回归分析构建了铜死亡随机森林 Cox 评分。随后，通过 KM 和 ROC 方法分析来自 GEO 和 ICGC 的独立队列的数据，评估了 CRFCS 的预后预测能力。此外，评估了 CRFCS 在 HCC 中的突变特征、免疫细胞浸润、免疫逃逸和药物敏感性。
基于四个铜死亡相关基因的泛化特征构建了铜死亡随机森林 Cox 评分。高 CRFCS 组患者的总体生存率较低。单变量多变量 Cox 回归分析验证了 CRFCS 是一个独立的预后指标。ROC 分析表明，CRFCS 是 HCC 的一个很好的预测指标（AUC=0.82）。突变分析表明，高 CRFCS 组的微卫星不稳定性（MSI）显著增加。同时，肿瘤微环境分析表明，高 CRFCS 组的免疫细胞浸润明显多于低 CRFCS 组。免疫逃逸评估分析表明，高 CRFCS 组的 TIDE 评分较低，表明高 CRFCS 组的免疫逃逸概率低于低 CRFCS 组。有趣的是，高 CRFCS 组中免疫检查点表达较高。药物敏感性分析表明，高 CRFCS 组的 HCC 患者索拉非尼的 IC 低于低 CRFCS 组。
在这项研究中，我们构建了一个铜死亡随机森林 Cox 评分（CRFCS）模型。CRFCS 被证明是 HCC 的一个有潜力的独立预后指标，高 CRFCS 样本显示预后不良。有趣的是，CRFCS 与 TME 特征以及临床治疗效果相关。重要的是，与低 CRFCS 组相比，高 CRFCS 组可能受益于免疫治疗和索拉非尼治疗。
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