Table1_Identification of a Pyroptosis-Related Gene Signature for Predicting the Immune Status and Prognosis in Lung Adenocarcinoma.XLSX

Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.

研究背景：细胞焦亡（pyroptosis）是一种由细胞膜破裂与炎性物质释放所触发的程序性细胞死亡形式，在癌症的发生与发展中发挥关键作用。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，但细胞焦亡在肺腺癌（lung adenocarcinoma, LUAD）中的具体作用仍尚不明确。本研究旨在探讨肺腺癌（LUAD）中细胞焦亡相关基因（pyroptosis-related genes, PRGs）的预后价值及其与肿瘤免疫微环境（tumor immune microenvironment, TIME）的关联。
研究方法：从癌症基因组图谱（The Cancer Genome Atlas, TCGA）与基因表达综合数据库（Gene Expression Omnibus, GEO）下载基因表达谱与临床信息。本研究在训练集中构建细胞焦亡相关基因预后特征，并在验证集中对该特征进行验证。随后开展细胞焦亡相关基因的功能富集分析与肿瘤免疫微环境分析，并基于风险评分与临床特征构建列线图。此外，本研究通过定量实时聚合酶链反应（quantitative real-time PCR, qRT-PCR）验证了肺腺癌的潜在生物标志物。
研究结果：本研究构建了基于5个细胞焦亡相关基因的预后特征，将肺腺癌患者分为高风险组与低风险组。高风险组患者的预后较低风险组更差。经Cox回归分析证实该特征为独立预后因素，且其受试者工作特征曲线（receiver operating characteristic, ROC）下面积（AUC）达0.677，为所有特征中最高。功能富集分析与肿瘤免疫微环境分析结果显示，两组亚组的免疫状态存在显著差异，且高风险组患者可能从免疫治疗中获益。此外，定量实时聚合酶链反应验证结果显示，血清PRKACA与GPX4可作为肺腺癌的诊断生物标志物。
研究结论：综上，本研究构建了基于5个细胞焦亡相关基因的风险特征，为阐明肺腺癌患者预后与生存的影响因素提供了全新视角，同时为个体化治疗方案的开发提供了理论依据。