Department of Colorectal and Anal Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, China.
J Cell Mol Med. 2022 Sep;26(17):4698-4709. doi: 10.1111/jcmm.17494. Epub 2022 Jul 24.
Necroptosis is a programmed necrosis in a caspase-independent fashion. The role of necroptosis-related genes (NRGs) in lung cancer remains unknow. Herein, we classified TCGA-LUAD cohort into two necroptosis-related subtypes (C1 and C2) by consensus clustering analysis. The result showed that subtype C1 had a favourable prognosis and higher infiltration levels of immune cells. Moreover, subtype C1 was more activated in immune-associated pathways. Then, we established an NRG prognosis model (NRG score) composed of six NRGs (RIPK3, MLKL, TLR2, TLR4, TNFRSF1A, NDRG2) and divided the cohort into low- and high-risk group. We found that the NRG score was associated with prognosis, tumour immune microenvironment and tumour mutation burden. We also constructed an accurate nomogram model to improve the clinical applicability of NRG score. The result indicated that NRG score may be an independent prognostic marker for lung cancer patients. Taken together, we established a prognosis model that may deepen the understanding of NRGs in lung cancer and provide a basis for developing more effective immunotherapy strategies.
细胞坏死是一种非胱天蛋白酶依赖的程序性细胞坏死。坏死相关基因(NRGs)在肺癌中的作用尚不清楚。在此,我们通过共识聚类分析将 TCGA-LUAD 队列分为两个坏死相关亚型(C1 和 C2)。结果表明,亚型 C1 具有良好的预后和更高水平的免疫细胞浸润。此外,亚型 C1 在免疫相关途径中更为活跃。然后,我们建立了一个由 6 个 NRGs(RIPK3、MLKL、TLR2、TLR4、TNFRSF1A、NDRG2)组成的 NRG 预后模型(NRG 评分),并将队列分为低风险组和高风险组。我们发现 NRG 评分与预后、肿瘤免疫微环境和肿瘤突变负荷有关。我们还构建了一个准确的列线图模型,以提高 NRG 评分的临床适用性。结果表明,NRG 评分可能是肺癌患者的独立预后标志物。综上所述,我们建立了一个预后模型,可能加深对 NRGs 在肺癌中的作用的理解,并为开发更有效的免疫治疗策略提供依据。