Yang Weichang, Li Zhouhua, Wang Wenjun, Wu Juan, Li Jinbo, Huang Xiaotian, Zhang Xinyi, Ye Xiaoqun
Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Front Genet. 2023 Jun 7;14:1206141. doi: 10.3389/fgene.2023.1206141. eCollection 2023.
Lung cancer has a high incidence and mortality rate worldwide. Vasculogenic mimicry (VM) is a specific modality of tumor angiogenesis that could potentially be a new target for tumor therapy. The purpose of this study was to explore the role of VM-related genes in assessing the prognosis and immune landscape of lung cancer. VM-related genes were obtained from previous studies, and the expression data and clinical data of lung adenocarcinoma (LUAD) patients were obtained from the TCGA database and GEO database. We performed enrichment analysis of 24 VM-related genes and screened hub genes by constructing a protein-protein interaction network and using Cytoscape software. Subsequently, we developed the VM score based on univariate Cox regression analysis and Lasso analysis and validated the VM score on the GSE72094 dataset. In addition, we constructed a nomogram based on the VM score in the TCGA cohort. Finally, we explored the correlation between the VM score and the tumor microenvironment, immune cell infiltration, immune checkpoints, and drug sensitivity. Enrichment analysis revealed that VM-related genes were associated with the HIF signaling pathway and angiogenic pathway. We developed a VM score based on 3 genes (EPHA2, LAMC2 and LOXL2) in LUAD patients. Kaplan-Meier analysis showed that the VM score was associated with poor prognosis in LUAD patients. The receiver operating characteristic curve suggested that the VM score and nomogram are valid predictors for the overall survival of LUAD patients. The VM score was significantly correlated with immune cell infiltration, such as naïve B cells, neutrophils, and eosinophils, and there was a difference in the TME between the high VM score group and the low VM score group. LUAD patients in the high VM score group were more sensitive to antitumor drugs. In summary, the VM score developed in this study is a valuable indicator for evaluating the prognosis and immune landscape of LUAD patients. VM may be a potential target for antitumor therapy in lung cancer.
肺癌在全球范围内具有较高的发病率和死亡率。血管生成拟态（VM）是肿瘤血管生成的一种特殊形式，有可能成为肿瘤治疗的新靶点。本研究的目的是探讨VM相关基因在评估肺癌预后和免疫格局中的作用。从先前的研究中获取VM相关基因，并从TCGA数据库和GEO数据库中获取肺腺癌（LUAD）患者的表达数据和临床数据。我们对24个VM相关基因进行了富集分析，并通过构建蛋白质-蛋白质相互作用网络和使用Cytoscape软件筛选出枢纽基因。随后，我们基于单变量Cox回归分析和Lasso分析开发了VM评分，并在GSE72094数据集上验证了VM评分。此外，我们在TCGA队列中基于VM评分构建了列线图。最后，我们探讨了VM评分与肿瘤微环境、免疫细胞浸润、免疫检查点和药物敏感性之间的相关性。富集分析表明，VM相关基因与HIF信号通路和血管生成通路相关。我们基于LUAD患者的3个基因（EPHA2、LAMC2和LOXL2）开发了VM评分。Kaplan-Meier分析表明，VM评分与LUAD患者的不良预后相关。受试者工作特征曲线表明，VM评分和列线图是LUAD患者总生存的有效预测指标。VM评分与幼稚B细胞、中性粒细胞和嗜酸性粒细胞等免疫细胞浸润显著相关，高VM评分组和低VM评分组之间的肿瘤微环境存在差异。高VM评分组的LUAD患者对抗肿瘤药物更敏感。总之，本研究开发的VM评分是评估LUAD患者预后和免疫格局的有价值指标。VM可能是肺癌抗肿瘤治疗的潜在靶点。
