Vasculogenic Mimicry Score Identifies the Prognosis and Immune Landscape of Lung Adenocarcinoma

Overview

Journal Front Genet

Date 2023 Jun 23

PMID 37351348

Authors

Weichang Yang

Zhouhua Li

Wenjun Wang

Juan Wu

Jinbo Li

Xiaotian Huang

Xinyi Zhang

Xiaoqun Ye

Affiliations

Soon will be listed here.

Abstract

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.

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References

Liu X, Zhang Q, Mu Y, Zhang X, Sai K, Pang J . Clinical significance of vasculogenic mimicry in human gliomas. J Neurooncol. 2011; 105(2):173-9. PMC: 3198193. DOI: 10.1007/s11060-011-0578-5. View

Quail D, Amulic B, Aziz M, Barnes B, Eruslanov E, Fridlender Z . Neutrophil phenotypes and functions in cancer: A consensus statement. J Exp Med. 2022; 219(6). PMC: 9086501. DOI: 10.1084/jem.20220011. View

Cao Z, Bao M, Miele L, Sarkar F, Wang Z, Zhou Q . Tumour vasculogenic mimicry is associated with poor prognosis of human cancer patients: a systemic review and meta-analysis. Eur J Cancer. 2013; 49(18):3914-23. DOI: 10.1016/j.ejca.2013.07.148. View

Siegel R, Miller K, Jemal A . Cancer statistics, 2019. CA Cancer J Clin. 2019; 69(1):7-34. DOI: 10.3322/caac.21551. View

Ruf W, Seftor E, Petrovan R, Weiss R, Gruman L, Margaryan N . Differential role of tissue factor pathway inhibitors 1 and 2 in melanoma vasculogenic mimicry. Cancer Res. 2003; 63(17):5381-9. View

Wu F, Wang L, Zhou C . Lung cancer in China: current and prospect. Curr Opin Oncol. 2020; 33(1):40-46. DOI: 10.1097/CCO.0000000000000703. View

Chen P, Liu Y, Wen Y, Zhou C . Non-small cell lung cancer in China. Cancer Commun (Lond). 2022; 42(10):937-970. PMC: 9558689. DOI: 10.1002/cac2.12359. View

Xia Y, Cai X, Fan J, Zhang L, Ren J, Li Z . The role of sema4D in vasculogenic mimicry formation in non-small cell lung cancer and the underlying mechanisms. Int J Cancer. 2018; 144(9):2227-2238. DOI: 10.1002/ijc.31958. View

Xu X, Zong Y, Gao Y, Sun X, Zhao H, Luo W . VEGF Induce Vasculogenic Mimicry of Choroidal Melanoma through the PI3k Signal Pathway. Biomed Res Int. 2019; 2019:3909102. PMC: 6657640. DOI: 10.1155/2019/3909102. View

10.

Lim Z, Ma P . Emerging insights of tumor heterogeneity and drug resistance mechanisms in lung cancer targeted therapy. J Hematol Oncol. 2019; 12(1):134. PMC: 6902404. DOI: 10.1186/s13045-019-0818-2. View

11.

Andreucci E, Peppicelli S, Ruzzolini J, Bianchini F, Calorini L . Physicochemical aspects of the tumour microenvironment as drivers of vasculogenic mimicry. Cancer Metastasis Rev. 2022; 41(4):935-951. PMC: 9758104. DOI: 10.1007/s10555-022-10067-x. View

12.

Delgado-Bellido D, Serrano-Saenz S, Fernandez-Cortes M, Oliver F . Vasculogenic mimicry signaling revisited: focus on non-vascular VE-cadherin. Mol Cancer. 2017; 16(1):65. PMC: 5359927. DOI: 10.1186/s12943-017-0631-x. View

13.

Lee M, Cho H, Park K, Jung H . ELK3 Controls Gastric Cancer Cell Migration and Invasion by Regulating ECM Remodeling-Related Genes. Int J Mol Sci. 2022; 23(7). PMC: 8998440. DOI: 10.3390/ijms23073709. View

14.

Kim H, Won Y, Shim J, Kim H, Kim J, Hong H . Morphological characteristics of vasculogenic mimicry and its correlation with EphA2 expression in gastric adenocarcinoma. Sci Rep. 2019; 9(1):3414. PMC: 6399224. DOI: 10.1038/s41598-019-40265-7. View

15.

Wechman S, Emdad L, Sarkar D, Das S, Fisher P . Vascular mimicry: Triggers, molecular interactions and in vivo models. Adv Cancer Res. 2020; 148:27-67. PMC: 7594199. DOI: 10.1016/bs.acr.2020.06.001. View

16.

Wei J, Hu M, Huang K, Lin S, Du H . Roles of Proteoglycans and Glycosaminoglycans in Cancer Development and Progression. Int J Mol Sci. 2020; 21(17). PMC: 7504257. DOI: 10.3390/ijms21175983. View

17.

Ishikawa M, Miyahara R, Sonobe M, Horiuchi M, Mennju T, Nakayama E . Higher expression of EphA2 and ephrin-A1 is related to favorable clinicopathological features in pathological stage I non-small cell lung carcinoma. Lung Cancer. 2012; 76(3):431-8. DOI: 10.1016/j.lungcan.2011.12.004. View

18.

Wu L, Zhu Y . The function and mechanisms of action of LOXL2 in cancer (Review). Int J Mol Med. 2015; 36(5):1200-4. DOI: 10.3892/ijmm.2015.2337. View

19.

Yang J, Liao Y, Mai D, Xie P, Qiang Y, Zheng L . Tumor vasculogenic mimicry predicts poor prognosis in cancer patients: a meta-analysis. Angiogenesis. 2016; 19(2):191-200. DOI: 10.1007/s10456-016-9500-2. View

20.

Ren S, Xiong X, You H, Shen J, Zhou P . The Combination of Immune Checkpoint Blockade and Angiogenesis Inhibitors in the Treatment of Advanced Non-Small Cell Lung Cancer. Front Immunol. 2021; 12:689132. PMC: 8206805. DOI: 10.3389/fimmu.2021.689132. View