Pan-cancer dissection of vasculogenic mimicry characteristic to provide potential therapeutic targets

作者全名:Tang, Haibin; Chen, Liuxun; Liu, Xvdong; Zeng, Shengjie; Tan, Hao; Chen, Gang

作者地址:[Tang, Haibin; Chen, Gang] Chongqing Med Univ, Affiliated Hosp 1, Dept Urol, Chongqing, Peoples R China; [Chen, Liuxun; Zeng, Shengjie] Chongqing Med Univ, Affiliated Hosp 2, Dept Urol, Chongqing, Peoples R China; [Liu, Xvdong] Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiothorac Surg, Chongqing, Peoples R China; [Tan, Hao] Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped, Chongqing, Peoples R China

通信作者:Chen, G (通讯作者),Chongqing Med Univ, Affiliated Hosp 1, Dept Urol, Chongqing, Peoples R China.

来源:FRONTIERS IN PHARMACOLOGY

ESI学科分类:PHARMACOLOGY & TOXICOLOGY

WOS号:WOS:001209848600001

JCR分区:Q1

影响因子:4.4

年份:2024

卷号:15

期号: 

开始页: 

结束页: 

文献类型:Article

关键词:vasculogenic mimicry; therapy target; immunotherapy; tumor microenvironment; immunosuppressive microenvironment; pan cancer analysis

摘要:Introduction: Vasculogenic mimicry (VM) represents a novel form of tumor angiogenesis that is associated with tumor invasiveness and drug resistance. However, the VM landscape across cancer types remains poorly understood. In this study, we elucidate the characterizations of VM across cancers based on multi-omics data and provide potential targeted therapeutic strategies.Methods: Multi-omics data from The Cancer Genome Atlas was used to conduct comprehensive analyses of the characteristics of VM related genes (VRGs) across cancer types. Pan-cancer vasculogenic mimicry score was established to provide a depiction of the VM landscape across cancer types. The correlation between VM and cancer phenotypes was conducted to explore potential regulatory mechanisms of VM. We further systematically examined the relationship between VM and both tumor immunity and tumor microenvironment (TME). In addition, cell communication analysis based on single-cell transcriptome data was used to investigate the interactions between VM cells and TME. Finally, transcriptional and drug response data from the Genomics of Drug Sensitivity in Cancer database were utilized to identify potential therapeutic targets and drugs. The impact of VM on immunotherapy was also further clarified.Results: Our study revealed that VRGs were dysregulated in tumor and regulated by multiple mechanisms. Then, VM level was found to be heterogeneous among different tumors and correlated with tumor invasiveness, metastatic potential, malignancy, and prognosis. VM was found to be strongly associated with epithelial-mesenchymal transition (EMT). Further analyses revealed cancer-associated fibroblasts can promote EMT and VM formation. Furthermore, the immune-suppressive state is associated with a microenvironment characterized by high levels of VM. VM score can be used as an indicator to predict the effect of immunotherapy. Finally, seven potential drugs targeting VM were identified.Conclusion: In conclusion, we elucidate the characteristics and key regulatory mechanisms of VM across various cancer types, underscoring the pivotal role of CAFs in VM. VM was further found to be associated with the immunosuppressive TME. We also provide clues for the research of drugs targeting VM. Our study provides an initial overview and reference point for future research on VM, opening up new avenues for therapeutic intervention.

基金机构:Chongqing Municipal Health Commission10.13039/100016834

基金资助正文:We would like to thank the staff members of the TCGA Research Network, the UCSC Xena data portal, and the TISCH data portal; as well as all the authors for making their valuable research data available.