Gong Zetian, Li Qifan, Yang Jian, Zhang Pengpeng, Sun Wei, Ren Qianhe, Tang Junjie, Wang Wei, Gong Hui, Li Jun
Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
Front Bioeng Biotechnol. 2022 May 12;10:852734. doi: 10.3389/fbioe.2022.852734. eCollection 2022.
Pyroptosis is a form of programmed cell death triggered by the rupture of cell membranes and the release of inflammatory substances; it is essential in the occurrence and development of cancer. A considerable number of studies have revealed that pyroptosis is closely associated to the biological process of several cancers. However, the role of pyroptosis in lung adenocarcinoma (LUAD) remains elusive. The purpose of this study was to explore the prognostic role of pyroptosis-related genes (PRGs) and their relationship with the tumor immune microenvironment (TIME) in LUAD. Gene expression profiles and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A prognostic PRG signature was established in the training set and verified in the validation sets. Functional enrichment and immune microenvironment analyses related to PRGs were performed and a nomogram based on the risk score and clinical characteristics was established. What is more, quantitative real-time PCR (qRT-PCR) analysis was applied in order to verify the potential biomarkers for LUAD. A prognostic signature based on five PRGs was constructed to separate LUAD patients into two risk groups. Patients in the high-risk group had worse prognoses than those in the low-risk group. The signature was identified as independent via Cox regression analyses and obtained the largest area under the curve (AUC = 0.677) in the receiver operating characteristic (ROC). Functional enrichment and immune microenvironment analyses demonstrated that the immune status was significantly different in the two subgroups and that immunotherapy may be effective for the high-risk group. Furthermore, qRT-PCR analysis verified that serum PRKACA and GPX4 could serve as diagnostic biomarkers for LUAD. Overall, a risk signature based on five PRGs was generated, providing a novel perspective on the determinants of prognosis and survival in LUAD, as well as a basis for the development of individualized regimes.
细胞焦亡是一种由细胞膜破裂和炎性物质释放引发的程序性细胞死亡形式；它在癌症的发生和发展过程中至关重要。大量研究表明，细胞焦亡与多种癌症的生物学过程密切相关。然而，细胞焦亡在肺腺癌（LUAD）中的作用仍不明确。本研究的目的是探讨细胞焦亡相关基因（PRGs）在LUAD中的预后作用及其与肿瘤免疫微环境（TIME）的关系。从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）下载基因表达谱和临床信息。在训练集中建立预后PRG特征，并在验证集中进行验证。对与PRGs相关的功能富集和免疫微环境进行分析，并基于风险评分和临床特征建立列线图。此外，应用定量实时PCR（qRT-PCR）分析来验证LUAD的潜在生物标志物。构建了基于五个PRGs的预后特征，将LUAD患者分为两个风险组。高风险组患者的预后比低风险组患者更差。通过Cox回归分析确定该特征具有独立性，并在受试者工作特征（ROC）曲线中获得最大曲线下面积（AUC = 0.677）。功能富集和免疫微环境分析表明，两个亚组的免疫状态存在显著差异，免疫治疗可能对高风险组有效。此外，qRT-PCR分析验证血清PRKACA和GPX4可作为LUAD的诊断生物标志物。总体而言，生成了基于五个PRGs的风险特征，为LUAD预后和生存的决定因素提供了新的视角，也为个体化治疗方案的制定提供了依据。
