基于PANoptosis基因的分子亚型及其在皮肤黑色素瘤中的免疫浸润特征。
Molecular Subtypes Based on PANoptosis Genes and Characteristics of Immune Infiltration in Cutaneous Melanoma.
发表日期：2023 Aug 31
作者：
Like Zhong, Wenkang Qian, Wangang Gong, Li Zhu, Xu Wang
来源：
MOLECULAR & CELLULAR PROTEOMICS
摘要：
黑色素瘤（CM）仍然是皮肤癌中最具威胁性的形式。进一步的风险分层和对CM的新预后靶点的寻找对临床具有积极意义。PANoptosis被定义为由PANoptosome复合物介导的炎症性程序性细胞死亡，不能仅仅通过火球症、凋亡或坏死症来描述。尽管PANoptosis与包括癌症在内的许多疾病密切相关，但该现象在CM中尚未报告。结合GTEx和TCGA数据库，我们提取了14个与PANoptosis相关的基因（PAGs）。然后，通过PAGs分析了CM的分子亚型及其与免疫微环境和免疫治疗反应性的关联。对与PAGs相关的差异表达基因进行LASSO和单因素Cox分析，以建立能够有效预测CM患者预后的PAGs特征。进一步利用免疫浸润、肿瘤突变负荷分析、免疫治疗反应和药物敏感性分析来进一步分析预后差异的原因。我们的研究为PANoptosis在CM中的作用提供了一个新的视角。
Cutaneous melanoma (CM) remains the most life-threatening form of skin cancer. Further risk stratification and search for new prognostic targets for CM are of positive clinical significance. PANoptosis is defined as an inflammatory programmed cell death mediated by the PANoptosome complex and cannot be characterized by pyroptosis, apoptosis or necroptosis alone. Although PANoptosis is closely associated with many diseases including cancer, it has not been reported in CM. Combined with GTEx and TCGA database, we extracted 14 PANoptosis-related genes (PAGs). The molecular subtypes of CM were then analyzed by PAGs and their associations with the immune microenvironment and immunotherapy reactivity were analyzed. LASSO and univariate Cox analysis was performed on PAGs-related differentially expressed genes to establish PAGs characteristics that could effectively predict the prognosis of CM patients. Immune infiltration, tumor mutation burden analysis, immunotherapy response and drug sensitivity analysis were used to further analyze the causes of prognostic differences. Our study provides a new perspective on the role of PANoptosis in CM.