The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, Guangdong, China 524023.
The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang, Guangdong, China 524023.
Oxid Med Cell Longev. 2022 Aug 31;2022:1749111. doi: 10.1155/2022/1749111. eCollection 2022.
Non-small-cell lung cancer (NSCLC) has a high incidence and mortality worldwide. Moreover, it needs more accurate means for predicting prognosis and treatments. Pyroptosis is a novel form of cell death about inflammation which was highly related to the occurrence and development of tumors. Despite having some studies about pyroptosis-related genes (PRGs) and cancer, the correlation has not been explored enough between PRGs and immune in NSCLC. In this study, we constructed a PRG model by WGCNA to access the prognosis value PRGs have. The testing cohort ( = 464) with four datasets from the GEO database conducted a survival analysis to confirm the stability of the prognostic model. The risk score and age are examined as independent prognostic factors. Based on the PRGs, we found multiple pathways enriched in immune in NSCLC. Separating samples into three subtypes by consensus cluster analysis, Cluster 3 was identified as immune-inflamed phenotype with an optimistic prognostic outcome. A three-gene PRG signature (BNIP3, CASP9, and CAPN1) was identified, and BNIP3 was identified as the core gene. Knockdown of BNIP3 significantly inhibited the growth of H358 cells and induced pyroptosis. In conclusion, the model construction based on PRGs provides novel insights into the prediction of NSCLC prognosis, and BNIP3 can serve as a diagnostic biomarker for NSCLC.
非小细胞肺癌(NSCLC)在全球范围内具有较高的发病率和死亡率。此外,它需要更准确的方法来预测预后和治疗效果。细胞焦亡是一种新型的炎症相关细胞死亡形式,与肿瘤的发生和发展密切相关。尽管已经有一些关于细胞焦亡相关基因(PRGs)与癌症的研究,但 PRGs 与 NSCLC 中的免疫之间的相关性尚未得到充分探索。在本研究中,我们通过 WGCNA 构建了一个 PRG 模型,以评估 PRGs 的预后价值。使用来自 GEO 数据库的四个数据集对测试队列(n=464)进行了生存分析,以确认预后模型的稳定性。风险评分和年龄被检验为独立的预后因素。基于 PRGs,我们发现了 NSCLC 中多个与免疫相关的富集通路。通过共识聚类分析将样本分为三个亚型,发现第 3 组为免疫激活表型,具有乐观的预后结果。鉴定出一个由三个基因组成的 PRG 特征(BNIP3、CASP9 和 CAPN1),其中 BNIP3 被鉴定为核心基因。敲低 BNIP3 显著抑制了 H358 细胞的生长并诱导了细胞焦亡。总之,基于 PRGs 的模型构建为 NSCLC 的预后预测提供了新的见解,BNIP3 可以作为 NSCLC 的诊断生物标志物。