Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Guangzhou Municipal Research Institute of Clinical Medicine, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, China.
Sci Rep. 2023 Jun 19;13(1):9921. doi: 10.1038/s41598-023-36720-1.
Lung adenocarcinoma (LUAD) is one of the most common causes of cancer-related death. The role of pyroptosis in LUAD remains unclear. Our study aimed to identify a prognostic signature of pyroptosis-related genes (PRGs) and explore the connection of PRGs with the tumour microenvironment in LUAD. Gene expression and clinical information were obtained from The Cancer Genome Atlas database. Consensus clustering was applied to classify LUAD patients. The least absolute shrinkage and selection operator Cox and multivariate Cox regression models were used to generate a PRG-related prognostic signature. The correlations between PRGs and tumour-infiltrating immune cells or the tumour mutational burden were analysed by Spearman's correlation analysis. In this study, 44 PRGs significantly differed in expression between LUAD and normal tissues. Based on these genes, patients were clustered into three clusters with significantly different distributions of tumour-infiltrating immune cells and immune checkpoint regulators. A total of four PRGs (NLRP1, HMGB1, CYCS, and BAK1) were used to construct a prognostic model. Significant correlations were observed between these prognostic PRGs and immune cell infiltration or the tumour mutational burden. Predictive nomogram results showed that BAK1 could be an independent prognostic biomarker in LUAD. Additionally, the expression level of BAK1 was validated in two independent Gene Expression Omnibus cohorts. Our identified prognostic PRG signature may provide insight for future studies targeting pyroptosis and the tumour microenvironment in LUAD. Future studies are needed to verify our current findings.
肺腺癌 (LUAD) 是癌症相关死亡的最常见原因之一。细胞焦亡在 LUAD 中的作用尚不清楚。本研究旨在鉴定与细胞焦亡相关基因 (PRGs) 的预后特征，并探讨 PRGs 与 LUAD 肿瘤微环境的关系。从癌症基因组图谱数据库中获取基因表达和临床信息。采用共识聚类对 LUAD 患者进行分类。最小绝对收缩和选择算子 Cox 和多变量 Cox 回归模型用于生成 PRG 相关的预后特征。通过 Spearman 相关分析分析 PRGs 与肿瘤浸润免疫细胞或肿瘤突变负担之间的相关性。在本研究中，44 个 PRGs 在 LUAD 和正常组织之间的表达存在显著差异。基于这些基因，患者被聚类为三个具有明显不同肿瘤浸润免疫细胞和免疫检查点调节剂分布的簇。共使用 4 个 PRGs（NLRP1、HMGB1、CYCS 和 BAK1）构建预后模型。这些预后 PRGs 与免疫细胞浸润或肿瘤突变负担之间存在显著相关性。预测列线图结果表明，BAK1 可能是 LUAD 的一个独立预后生物标志物。此外，在两个独立的基因表达综合数据集队列中验证了 BAK1 的表达水平。我们鉴定的预后 PRG 特征可能为 LUAD 中针对细胞焦亡和肿瘤微环境的未来研究提供思路。需要进一步的研究来验证我们目前的发现。
