血管内皮生长因子 D 在肺腺癌免疫治疗反应中的作用。
Role of vascular endothelial growth factor D in lung adenocarcinoma immunotherapy response.
发表日期:2024
作者:
Xiaoling Du, Sha Yang, Jiaojiao Bian, Ying Zhang, Yuquan Wang, Zhan Lv
来源:
Cell Death & Disease
摘要:
鉴定与肿瘤相关巨噬细胞 (TAM)、肿瘤免疫治疗和肺腺癌 (LUAD) 预后相关的关键基因。LUAD 样本的 mRNA 表达谱来自癌症基因组图谱 (TCGA) 数据库。使用“CIBERSORT”R包来计算肿瘤和邻近正常组织中先天免疫细胞浸润的比例。使用加权基因相关网络分析 (WGCNA)、最小绝对收缩和选择算子 (LASSO) 以及多元 Cox 回归分析 (COX) 确定 LUAD 中的 TAM 相关基因,以构建预后风险模型。 IMvigor210 队列用于验证这些基因作为免疫治疗反应预测因子的作用。采用组织微阵列、免疫荧光染色和mRNA水平检测方法确定LUAD组织中危险因素的相关性。CIBERSORT分析显示肿瘤与癌旁组织之间先天免疫细胞存在显着差异。从 WGCNA 中鉴定出与这些细胞相关的 74 个差异基因。 TAM预后模型中的四个中心基因(B型内皮素受体、血管内皮生长因子D(VEGFD)、潜在转化生长因子β结合蛋白4(LTBP4)和成纤维细胞生长因子受体4(FGFR4))被确定为独立的预后基因危险因素(P < 0.05)。 VEGFD表达被确定为LUAD预后预测的低危因素(P < 0.05)。此外,与高危患者相比,低危患者对抗PD-L1治疗表现出更高的敏感性(P < 0.05)。 VEGFD 水平与程序性细胞死亡 1 (PD-1) 水平呈负相关(r = -0.363;P < 0.05),表明 VEGFD 可以作为抗 PD-1 治疗的预测因子。 VEGFD 与先天免疫相关。 LUAD,它可以预测 LUAD 预后,因此可能是 LUAD 患者抗 PD-1 治疗的潜在预测因子。AJTR 版权所有 © 2024。
To identify key genes associated with tumor-associated macrophages (TAMs), tumor immunotherapy, in the prognosis of lung adenocarcinoma (LUAD).The mRNA expression profiles of LUAD samples were obtained from The Cancer Genome Atlas (TCGA) database. The "CIBERSORT" R package was employed to calculate the proportion of innate immune cell infiltration in both tumor and adjacent normal tissues. TAM-associated genes in LUAD were identified to construct a prognostic risk model using weighted gene correlation network analysis (WGCNA), Least Absolute Shrinkage and Selection Operator (LASSO), and multivariate Cox regression analyses (COX). The IMvigor210 cohort was utilized to validate the roles of these genes as predictors of immunotherapy response. Tissue microarrays, immunofluorescence staining, and mRNA level detection methods were used to determine the correlation of risk factors in LUAD tissues.CIBERSORT analysis revealed significant differences in innate immune cells between tumor and adjacent tissues. Seventy-four differential genes linked to these cells were identified from WGCNA. Four hub genes (endothelin receptor type B, vascular endothelial growth factor D (VEGFD), latent transforming growth factor beta binding protein 4 (LTBP4), and fibroblast growth factor receptor 4 (FGFR4)) in the TAM prognostic model were identified as independent prognostic risk factors (P < 0.05). VEGFD expression was identified as a low-risk factor for LUAD prognosis prediction (P < 0.05). Moreover, low-risk patients exhibited higher sensitivity to anti-PD-L1 therapy compared to high-risk patients (P < 0.05). VEGFD levels were negatively correlated with programmed cell death 1 (PD-1) levels (r = -0.363; P < 0.05), suggesting that VEGFD may serve as a predictor for anti-PD-1 treatment.VEGFD is associated with innate immunity in LUAD, it can predict LUAD prognosis, and therefor may be a potential predictor for anti-PD-1 treatment in patients with LUAD.AJTR Copyright © 2024.