Computational framework identifies contributing factors for differences between PANoptosis clusters in multiple cancer types

The importance of inflammatory cell death in cancer is increasingly being recognized as this type of death can promote or stall tumorigenesis depending on the cellular context. A unique form of inflammatory cell death, PANoptosis, has been shown to play a role in cancer proliferation in murine models. Further, a recent computational study has shown that, through pancancer transcriptomic profiling of genes involved in PANoptosis, patients can be stratified into PANoptosis High and PANoptosis Low cluster and this classification has significant differences in prognostic associations (overall survival) for low grade gliomas (LGG), kidney and renal cell carcinoma (KIRC) and skin cutaneous melanoma (SKCM) cancers . Here, we perform a comprehensive comparison of molecular characteristics including genetic, genomic, tumor microenvironment composition and immune activation, and pathway enrichments between PANoptosis High and PANoptosis Low clusters to determine their relevance in driving the differential prognostic associations for LGG, KIRC and SKCM cancers. By identifying various biological features, we can drive better prognostic implications for at risk stratified patient populations based on the PANoptosis phenotype in LGG, KIRC and SKCM cancers.

炎症细胞死亡在癌症中的重要性日益凸显，因为此类死亡根据细胞环境的不同，可能促进或抑制肿瘤的发生发展。一种独特的炎症细胞死亡形式——PANoptosis，已被证实能在小鼠模型中促进癌症增殖。此外，一项近期的研究表明，通过对参与PANoptosis的基因进行跨癌症转录组分析，患者可以被分为PANoptosis高表达群和PANoptosis低表达群，这种分类在低级别胶质瘤（LGG）、肾脏和肾细胞癌（KIRC）以及皮肤黑色素瘤（SKCM）的预后关联（总生存期）上存在显著差异。在此，我们对PANoptosis高表达群和PANoptosis低表达群之间的分子特征进行了全面比较，包括遗传学、基因组学、肿瘤微环境组成以及免疫激活，以及通路富集，以确定它们在驱动LGG、KIRC和SKCM癌症不同预后关联中的作用。通过识别各种生物学特征，我们能够基于LGG、KIRC和SKCM癌症中的PANoptosis表型，为具有风险分层的人群提供更佳的预后意义。