Vasculogenic mimicry score identifies the prognosis and immune landscape of lung adenocarcinoma

Weichang Yang; Zhouhua Li; Wenjun Wang; Juan Wu; Jinbo Li; Xiaotian Huang; Xinyi Zhang; Xiaoqun Ye

doi:10.3389/fgene.2023.1206141

Vasculogenic mimicry score identifies the prognosis and immune landscape of lung adenocarcinoma

Front Genet. 2023 Jun 7:14:1206141. doi: 10.3389/fgene.2023.1206141. eCollection 2023.

Authors

Weichang Yang¹, Zhouhua Li¹, Wenjun Wang¹, Juan Wu¹, Jinbo Li¹, Xiaotian Huang¹, Xinyi Zhang¹, Xiaoqun Ye¹

Affiliation

¹ Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Keywords: immune landscape; lung adenocarcinoma; prognosis; tumor microenvironment (TEM); vasculogenic mimicry.

Grants and funding

This study was supported by the National Natural Science Foundation of China (Grant No. 81660493), the National Clinical Research Center for Geriatrics-Jiangxi branch center, 2021ZDG02001, the Natural Science Foundation of Jiangxi Province (Grant No.20202ACBL206019), the cooperation project of the Science and Technology Department of Jiangxi province (No. 20212BDH81021) and the project of Health Commission of Jiangxi Province No.202210038.