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

Chunyu Zhang; Jiatong Xiao; Tong Yuan; Yunbo He; Dingshan Deng; Zicheng Xiao; Jinbo Chen; Xiongbing Zu; Peihua Liu; Zhi Liu

doi:10.3389/fphar.2023.1163115

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

Front Pharmacol. 2023 Apr 24:14:1163115. doi: 10.3389/fphar.2023.1163115. eCollection 2023.

Authors

Chunyu Zhang^{1

2}, Jiatong Xiao^{1

2}, Tong Yuan³, Yunbo He¹, Dingshan Deng¹, Zicheng Xiao¹, Jinbo Chen¹, Xiongbing Zu¹, Peihua Liu^{1

2}, Zhi Liu^{1

4}

Affiliations

¹ Departments of Urology, Xiangya Hospital, Central South University, Changsha, China.
² National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China.
³ Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Department of Urology, The Second Affiliated Hospital, Guizhou Medical University, Kaili, China.

Abstract

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.

Keywords: bladder cancer; immunotherapy; molecular subtype; tumor microenvironment; vasculogenic mimicry.

Grants and funding

A grant from the National Natural Science Foundation of China supported this research [82070785, 81873626], and the Science and Technology fund project of Health and Family Planning Commission of Guizhou province (No. gzwjkj2022-100). Basic Research Project of Science and Technology Cooperation in Qiandongnan Prefecture (No. 2023-16).