肝细胞癌（LIHC）是死亡率最高的恶性肿瘤之一，主要是由于化疗耐药最终导致治疗失败。尽管有影响，但针对 LIHC 患者的疾病进展、肿瘤微环境和药物敏感性的预测模型仍然难以捉摸。认识到各种程序性细胞死亡 (PCD) 模式对肿瘤进化的显着影响，本研究研究了 PCD 基因，以阐明它们对 LIHC 的预后和免疫景观的影响。为了开发分类和模型，我们总共采用了 17 个相关基因具有 PCD 图案。为了收集数据，我们从 TCGA 数据库（特别是 LIHC 患者）获取了基因表达谱、体细胞突变信息、拷贝数变异数据和相应的临床数据。此外，我们从基因表达综合（GEO）数据库中获得了空间转录组数据和其他批量数据集以进行进一步分析。进行了各种实验来验证 PCD 基因 PRKDC 在增殖、迁移、侵袭、EMT、细胞周期、治疗敏感性和抗肿瘤免疫中的作用。基于这些基因的新 LIHC 分类将患者分为两类：C1 和 C2。 C2 簇表现出预后不良和免疫激活微环境的特征。该组对免疫检查点抑制剂表现出更大的反应潜力，显示出更高水平的某些免疫特征和受体。使用 17 个选定的 PCD 基因构建程序性细胞死亡指数 (PCDI)。该指数可以有效预测患者的预后，PCDI越高表明生存率越差，微环境越有利于肿瘤。免疫景观揭示了与 PCDI 的不同相互作用，提示了治疗目标和对治疗耐药性的见解。此外，实验结果表明，PRKDC可以增强恶性细胞的侵袭性和生长，可以作为潜在的治疗靶点，为改善LIHC患者的预后带来希望。该研究揭示了程序性细胞死亡在预后中的见解和潜在的治疗干预措施。我们发现PRKDC可以作为增强抗肿瘤免疫功效的靶点，同时使肝癌化疗和靶向治疗增敏。

Liver hepatocellular carcinoma (LIHC) ranks among the malignancies with the highest mortality rates, primarily due to chemoresistance culminating in treatment failure. Despite its impact, predictive models addressing disease progression, tumor microenvironment, and drug sensitivity remain elusive for LIHC patients. Recognizing the significant influence of various programmed cell death (PCD) modes on tumor evolution, this study investigates PCD genes to elucidate their implications on the prognosis and immune landscape of LIHC.To develop the classification and model, we employed a total of 17 genes associated with PCD patterns. To collect data, we acquired gene expression profiles, somatic mutation information, copy number variation data, and corresponding clinical data from the TCGA database, specifically from LIHC patients. Moreover, we obtained spatial transcriptome data and additional bulk datasets from the Gene Expression Omnibus (GEO) database to conduct further analysis. Various experiments were conducted to validate the role of the PCD gene PRKDC in proliferation, migration, invasion, EMT, cell cycle, therapeutic sensitivity, and antitumor immunity.A novel LIHC classification based on these genes divided patients into two clusters, C1 and C2. The C2 cluster exhibited characteristics indicative of poor prognosis and an immune-activated microenvironment. This group showed greater response potential to immune checkpoint inhibitors, displaying higher levels of certain immune signatures and receptors. A programmed cell death index (PCDI) was constructed using 17 selected PCD genes. This index could effectively predict patient prognosis, with higher PCDI indicating poorer survival rates and a more pro-tumor microenvironment. Immune landscapes revealed varying interactions with PCDI, suggesting therapeutic targets and insights into treatment resistance. Moreover, experiments results suggested that PRKDC can augment the invasive nature and growth of malignant cells and it can serve as a potential target for therapy, offering hope for ameliorating the prognosis of LIHC patients.The study uncovers the insights of programmed cell death in the prognosis and potential therapeutic interventions. And we found that PRKDC can serve as a target for enhancing the efficacy of antitumor immunity while sensitizing chemotherapy and targeted therapy in liver hepatocellular carcinoma.