肿瘤细胞的非凋亡调节细胞死亡（RCD）深刻影响肿瘤进展，并在确定对免疫检查点抑制剂（ICIs）的反应中发挥关键作用。根据从数据库和文献中获得的 507 个非凋亡 RCD 基因的表达，通过共识聚类分析来鉴定预后独特的 HCC 亚型。同时，集成一套生物信息学工具来分析两种亚型内肿瘤免疫微环境浸润、基因突变、拷贝数变异和表观遗传学改变的差异。最后，构建了非凋亡 RCDRS 特征，并在 HCC 患者组织中评估了其可靠性。与低 RCDRS 亚组相比，高 RCDRS HCC 亚组的总生存率显着较低，对 ICI 的敏感性较低，但对顺铂、紫杉醇和索拉非尼的敏感性较高。总体而言，我们建立了一个由四个非凋亡 RCD 基因组成的 RCDRS 组合，这可能是评估 HCC 预后、指导治疗决策并最终改善患者预后的有希望的预测因子。© 2024 作者。

Non-apoptotic regulated cell death (RCD) of tumor cells profoundly affects tumor progression and plays critical roles in determining response to immune checkpoint inhibitors (ICIs). Prognosis-distinctive HCC subtypes were identified by consensus cluster analysis based on the expressions of 507 non-apoptotic RCD genes obtained from databases and literature. Meanwhile, a set of bioinformatic tools was integrated to analyze the differences of the tumor immune microenvironment infiltration, genetic mutation, copy number variation, and epigenetics alternations within two subtypes. Finally, a non-apoptotic RCDRS signature was constructed and its reliability was evaluated in HCC patients' tissues. The high-RCDRS HCC subgroup showed a significantly lower overall survival and less sensitivity to ICIs compared to low-RCDRS subgroup, but higher sensitivity to cisplatin, paclitaxel, and sorafenib. Overall, we established an RCDRS panel consisting of four non-apoptotic RCD genes, which might be a promising predictor for evaluating HCC prognosis, guiding therapeutic decision-making, and ultimately improving patient outcomes.© 2024 The Author(s).