Department of Cardiothoracic Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
Center for Experimental Medicine, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
Sci Rep. 2023 Oct 25;13(1):18226. doi: 10.1038/s41598-023-45289-8.
Lung adenocarcinoma (LUAD) remains an incurable disease with a poor prognosis. This study aimed to explore neutrophil‑related genes (NRGs) and develop a prognostic signature for predicting the prognosis of LUAD. NRGs were obtained by intersecting modular genes identified by weighted gene co-expression network analysis (WGCNA) using bulk RNA-seq data and the marker genes of neutrophils identified from single-cell RNA-sequencing(scRNA-seq) data. Univariate Cox regression, least absolute shrinkage and selection operator (LASSO), and multivariate Cox analyses were run to construct a prognostic signature, follow by delineation of risk groups, and external validation. Analyses of ESTIMAT, immune function, Tumor Immune Dysfunction and Exclusion (TIDE) scores, Immune cell Proportion Score (IPS), and immune checkpoint genes between high- and low-risk groups were performed, and then analyses of drug sensitivity to screen for sensitive anticancer drugs in high-risk groups. A total of 45 candidate NRGs were identified, of which PLTP, EREG, CD68, CD69, PLAUR, and CYP27A1 were considered to be significantly associated with prognosis in LUAD and were used to construct a prognostic signature. Correlation analysis showed significant differences in the immune landscape between high- and low-risk groups. In addition, our prognostic signature was important for predicting drug sensitivity in the high-risk group. Our study screened for NRGs in LUAD and constructed a novel and effective signature, revealing the immune landscape and providing more appropriate guidance protocols in LUAD treatment.
肺腺癌 (LUAD) 仍然是一种无法治愈的疾病，预后不良。本研究旨在探索中性粒细胞相关基因 (NRGs)，并开发一种预测 LUAD 预后的预后特征。通过使用批量 RNA-seq 数据的加权基因共表达网络分析 (WGCNA) 鉴定的模块基因与单细胞 RNA-seq(scRNA-seq) 数据中鉴定的中性粒细胞标记基因的交集获得 NRGs。进行单变量 Cox 回归、最小绝对收缩和选择算子 (LASSO) 和多变量 Cox 分析，以构建预后特征，然后划定风险组并进行外部验证。对 ESTIMAT、免疫功能、肿瘤免疫功能障碍和排除 (TIDE) 评分、免疫细胞比例评分 (IPS) 和高、低风险组之间的免疫检查点基因进行分析，然后分析药物敏感性以筛选高风险组中的敏感抗癌药物。确定了 45 个候选 NRGs，其中 PLTP、EREG、CD68、CD69、PLAUR 和 CYP27A1 被认为与 LUAD 的预后显著相关，并用于构建预后特征。相关性分析显示高、低风险组之间的免疫景观存在显著差异。此外，我们的预后特征对于预测高危组的药物敏感性很重要。我们的研究筛选了 LUAD 中的 NRGs，并构建了一个新的有效的特征，揭示了免疫景观，并为 LUAD 治疗提供了更合适的指导方案。
