肿瘤相关巨噬细胞中与分化相关的基因作为非小细胞肺癌潜在的预后生物标志物。
Differentiation-related genes in tumor-associated macrophages as potential prognostic biomarkers in non-small cell lung cancer.
机构信息
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
出版信息
Front Immunol. 2023 Mar 9;14:1123840. doi: 10.3389/fimmu.2023.1123840. eCollection 2023.
BACKGROUND
The purpose of this study was to evaluate the role of differentiation-related genes (DRGs) in tumor-associated macrophages (TAMs) in non-small cell lung cancer (NSCLC).
METHODS
Single cell RNA-seq (scRNA-seq) data from GEO and bulk RNA-seq data from TCGA were analyzed to identify DRGs using trajectory method. Functional gene analysis was carried out by GO/KEGG enrichment analysis. The mRNA and protein expression in human tissue were analyzed by HPA and GEPIA databases. To investigate the prognostic value of these genes, three risk score (RS) models in different pathological types of NSCLC were generated and predicted NSCLC prognosis in datasets from TCGA, UCSC and GEO databases.
RESULTS
1,738 DRGs were identified through trajectory analysis. GO/KEGG analysis showed that these genes were predominantly related to myeloid leukocyte activation and leukocyte migration. 13 DRGs () related to prognosis were obtained through univariate Cox analysis and Lasso regression. , , , , , , , , and were downregulated in NSCLC compared to non-cancer tissue. The mRNA of 13 genes were significantly expressed in pulmonary macrophages with strong cell specificity. Meanwhile, immunohistochemical staining showed that were expressed in different degrees in lung cancer tissues. (HR=1.4, P<0.05) and (HR=1.6, P<0.05) expression were associated with a worse prognosis in lung squamous cell carcinoma; (HR=0.64, P<0.05), (HR=0.65, P<0.05), (HR=0.71, P<0.05) and (HR=0.61, P<0.05) expression were associated with a better prognosis in lung adenocarcinoma. Three RS models based on 13 DRGs both showed that the high RS was significantly associated with poor prognosis in different pathological types of NSCLC.
CONCLUSIONS
This study highlights the prognostic value of DRGs in TAMs in NSCLC patients, providing novel insights for the development of therapeutic and prognostic targets based on TAM functional differences.
背景
本研究旨在评估分化相关基因（DRGs）在非小细胞肺癌（NSCLC）肿瘤相关巨噬细胞（TAMs）中的作用。
方法
使用轨迹方法分析 GEO 的单细胞 RNA-seq（scRNA-seq）数据和 TCGA 的批量 RNA-seq 数据，以鉴定 DRGs。通过 GO/KEGG 富集分析进行功能基因分析。通过 HPA 和 GEPIA 数据库分析人类组织中的 mRNA 和蛋白表达。为了研究这些基因的预后价值，在不同病理类型的 NSCLC 中生成了三个风险评分（RS）模型，并预测了 TCGA、UCSC 和 GEO 数据库中的 NSCLC 预后。
结果
通过轨迹分析鉴定了 1738 个 DRGs。GO/KEGG 分析表明，这些基因主要与髓样白细胞激活和白细胞迁移有关。通过单因素 Cox 分析和 Lasso 回归获得了 13 个与预后相关的 DRGs（）。与非癌组织相比，在 NSCLC 中， 、 、 、 、 、 、 、 、 和 下调。13 个基因的 mRNA 在肺巨噬细胞中表达具有很强的细胞特异性。同时，免疫组织化学染色显示，在不同程度上表达于肺癌组织中。 （HR=1.4，P<0.05）和 （HR=1.6，P<0.05）表达与肺鳞癌预后不良相关； （HR=0.64，P<0.05）、 （HR=0.65，P<0.05）、 （HR=0.71，P<0.05）和 （HR=0.61，P<0.05）表达与肺腺癌预后良好相关。基于 13 个 DRGs 的三个 RS 模型均表明，高 RS 与不同病理类型 NSCLC 的不良预后显著相关。
结论
本研究强调了 DRGs 在 NSCLC 患者 TAMs 中的预后价值，为基于 TAM 功能差异开发治疗和预后靶点提供了新的见解。
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