Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Department of General Practice, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Front Immunol. 2023 Aug 18;14:1218661. doi: 10.3389/fimmu.2023.1218661. eCollection 2023.
Previous studies have demonstrated that PANoptosis is strongly correlated with cancer immunity and progression. This study aimed to develop a PANoptosis-related signature (PANRS) to explore its potential value in predicting the prognosis and immunotherapy response of hepatocellular carcinoma (HCC).
Based on the expression of PANoptosis-related genes, three molecular subtypes were identified. To construct a signature, the differentially expressed genes between different molecular subtypes were subjected to multivariate least absolute shrinkage and selection operator Cox regression analyses. The risk scores of patients in the training set were calculated using the signature. The patients were classified into high-risk and low-risk groups based on the median risk scores. The predictive performance of the signature was evaluated using Kaplan-Meier plotter, receiving operating characteristic curves, nomogram, and calibration curve. The results were validated using external datasets. Additionally, the correlation of the signature with the immune landscape and drug sensitivity was examined. Furthermore, the effect of knockdown on HCC cell behavior was verified using experiments.
This study developed a PANRS. The risk score obtained by using the PANRS was an independent risk factor for the prognosis of patients with HCC and exhibited good prognostic predictive performance. The nomogram constructed based on the risk score and clinical information can accurately predicted the survival probability of patients with HCC. Patients with HCC in the high-risk groups have high immune scores and tend to generate an immunosuppressive microenvironment. They also exhibited a favorable response to immunotherapy, as evidenced by high tumor mutational burden, high immune checkpoint gene expression, high human leukocyte antigen gene expression, low tumor immune dysfunction and low exclusion scores. Additionally, the PANRS enabled the identification of 15 chemotherapeutic agents, including sorafenib, for patients with HCC with different risk levels, guiding clinical treatment. The signature gene was upregulated in HCC cell lines. knockdown markedly decreased HCC cell proliferation and migration.
PANRS can accurately predict the prognosis and immunotherapy response of patients with HCC and consequently guide individualized treatment.
先前的研究表明，PANoptosis 与癌症免疫和进展密切相关。本研究旨在开发一个 PANoptosis 相关的特征（PANRS），以探索其在预测肝细胞癌（HCC）预后和免疫治疗反应中的潜在价值。
基于 PANoptosis 相关基因的表达，确定了三个分子亚型。为了构建特征，对不同分子亚型之间的差异表达基因进行了多变量最小绝对收缩和选择算子 Cox 回归分析。使用该特征计算训练集中患者的风险评分。根据中位风险评分将患者分为高风险组和低风险组。使用 Kaplan-Meier plotter、接收者操作特征曲线、列线图和校准曲线评估特征的预测性能。使用外部数据集验证结果。此外，还研究了特征与免疫景观和药物敏感性的相关性。进一步通过 实验验证了特征与 HCC 细胞行为的相关性。
本研究开发了一个 PANRS。使用 PANRS 获得的风险评分是 HCC 患者预后的独立危险因素，具有良好的预后预测性能。基于风险评分和临床信息构建的列线图可以准确预测 HCC 患者的生存概率。高风险组的 HCC 患者具有较高的免疫评分，倾向于产生免疫抑制微环境。他们对免疫治疗也有较好的反应，表现为高肿瘤突变负荷、高免疫检查点基因表达、高人类白细胞抗原基因表达、低肿瘤免疫功能障碍和低排除评分。此外，PANRS 还可以识别出 15 种化疗药物，包括索拉非尼，用于不同风险水平的 HCC 患者，指导临床治疗。特征基因在 HCC 细胞系中上调。 敲低显著降低了 HCC 细胞的增殖和迁移。
PANRS 可以准确预测 HCC 患者的预后和免疫治疗反应，从而指导个体化治疗。
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