Molecular vasculogenic mimicry–Related signatures predict clinical outcomes and therapeutic responses in bladder cancer: Results from real-world cohorts

Frontiers in Pharmacology

Pharmacology

Jinbo Chen¹  Xiongbing Zu¹  Dingshan Deng¹  Zicheng Xiao¹  Yunbo He¹  Zhi Liu²  Chunyu Zhang³  Jiatong Xiao³  Peihua Liu³  Tong Yuan⁴ 

[1] Departments of Urology, Xiangya Hospital, Central South University, Changsha, China;Departments of Urology, Xiangya Hospital, Central South University, Changsha, China;Department of Urology, The Second Affiliated Hospital, Guizhou Medical University, Kaili, China;Departments of Urology, Xiangya Hospital, Central South University, Changsha, China;National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China;Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;

关键词: bladder cancer;    vasculogenic mimicry;    molecular subtype;    tumor microenvironment;    immunotherapy;   

DOI  :  10.3389/fphar.2023.1163115

 received in 2023-02-10, accepted in 2023-04-06,  发布年份 2023

来源: Frontiers

【 摘 要 】

Bladder cancer (BLCA) is a heterogeneous disease, and there are many classical molecular subtypes that reflect tumor immune microenvironment (TME) heterogeneity but their clinical utility is limited and correct individual treatment and prognosis cannot be predicted based on them. To find reliable and effective biomarkers and tools for predicting patients’ clinical responses to several therapies, we developed a new systemic indicator of molecular vasculogenic mimicry (VM)–related genes mediated by molecular subtypes based on the Xiangya cohort and additional external BLCA cohorts using a random forest algorithm. A correlation was then done between the VM_Score and classical molecular subtypes, clinical outcomes, immunophenotypes, and treatment options for BLCA. With the VM_Score, it is possible to predict classical molecular subtypes, immunophenotypes, prognosis, and therapeutic potential of BLCA with high accuracy. The VM_Scores of high levels indicate a more anticancer immune response but a worse prognosis due to a more basal and inflammatory phenotype. The VM_Score was also found associated with low sensitivity to antiangiogenic and targeted therapies targeting the FGFR3, β-catenin, and PPAR-γ pathways but with high sensitivity to cancer immunotherapy, neoadjuvant chemotherapy, and radiotherapy. A number of aspects of BLCA biology were reflected in the VM_Score, providing new insights into precision medicine. Additionally, the VM_Score may be used as an indicator of pan-cancer immunotherapy response and prognosis.

【 授权许可】

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Copyright © 2023 Zhang, Xiao, Yuan, He, Deng, Xiao, Chen, Zu, Liu and Liu.