Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.
Jiangsu Vocational College of Medicine, Yancheng, China.
Front Immunol. 2023 Jun 15;14:1197152. doi: 10.3389/fimmu.2023.1197152. eCollection 2023.
Hepatocellular carcinoma (HCC) is a highly prevalent and fatal cancer. The role of PANoptosis, a novel form of programmed cell death, in HCC is yet to be fully understood. This study focuses on identifying and analyzing PANoptosis-associated differentially expressed genes in HCC (HPAN_DEGs), aiming to enhance our understanding of HCC pathogenesis and potential treatment strategies.
We analyzed HCC differentially expressed genes from TCGA and IGCG databases and mapped them to the PANoptosis gene set, identifying 69 HPAN_DEGs. These genes underwent enrichment analyses, and consensus clustering analysis was used to determine three distinct HCC subgroups based on their expression profiles. The immune characteristics and mutation landscape of these subgroups were evaluated, and drug sensitivity was predicted using the HPAN-index and relevant databases.
The HPAN_DEGs were mainly enriched in pathways associated with the cell cycle, DNA damage, Drug metabolism, Cytokines, and Immune receptors. We identified three HCC subtypes (Cluster_1, SFN+PDK4-; Cluster_2, SFN-PDK4+; Cluster_3, SFN/PDK4 intermediate expression) based on the expression profiles of the 69 HPAN_DEGs. These subtypes exhibited distinct clinical outcomes, immune characteristics, and mutation landscapes. The HPAN-index, generated by machine learning using the expression levels of 69 HPAN_DEGs, was identified as an independent prognostic factor for HCC. Moreover, the high HPAN-index group exhibited a high response to immunotherapy, while the low HPAN-index group showed sensitivity to small molecule targeted drugs. Notably, we observed that the YWHAB gene plays a significant role in Sorafenib resistance.
This study identified 69 HPAN_DEGs crucial to tumor growth, immune infiltration, and drug resistance in HCC. Additionally, we discovered three distinct HCC subtypes and constructed an HPAN-index to predict immunotherapeutic response and drug sensitivity. Our findings underscore the role of YWHAB in Sorafenib resistance, presenting valuable insights for personalized therapeutic strategy development in HCC.
肝细胞癌（HCC）是一种高发且致命的癌症。PANoptosis（一种新形式的程序性细胞死亡）在 HCC 中的作用尚未完全理解。本研究旨在识别和分析 HCC 中与 PANoptosis 相关的差异表达基因（HPAN_DEGs），以增强我们对 HCC 发病机制和潜在治疗策略的理解。
我们分析了 TCGA 和 IGCG 数据库中的 HCC 差异表达基因，并将其映射到 PANoptosis 基因集，确定了 69 个 HPAN_DEGs。这些基因进行了富集分析，并基于其表达谱进行了共识聚类分析，确定了三个不同的 HCC 亚组。评估了这些亚组的免疫特征和突变景观，并使用 HPAN-index 和相关数据库预测了药物敏感性。
HPAN_DEGs 主要富集在与细胞周期、DNA 损伤、药物代谢、细胞因子和免疫受体相关的途径中。我们根据 69 个 HPAN_DEGs 的表达谱确定了三个 HCC 亚型（Cluster_1，SFN+PDK4-；Cluster_2，SFN-PDK4+；Cluster_3，SFN/PDK4 中间表达）。这些亚型表现出不同的临床结局、免疫特征和突变景观。使用 69 个 HPAN_DEGs 的表达水平通过机器学习生成的 HPAN-index 被确定为 HCC 的独立预后因素。此外，高 HPAN-index 组对免疫治疗有较高的反应，而低 HPAN-index 组对小分子靶向药物敏感。值得注意的是，我们观察到 YWHAB 基因在 Sorafenib 耐药中起重要作用。
本研究确定了 69 个对 HCC 肿瘤生长、免疫浸润和耐药性至关重要的 HPAN_DEGs。此外，我们发现了三个不同的 HCC 亚型，并构建了 HPAN-index 来预测免疫治疗反应和药物敏感性。我们的研究结果强调了 YWHAB 在 Sorafenib 耐药中的作用，为 HCC 的个体化治疗策略开发提供了有价值的见解。
