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BMC Cancer
Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Kidney Cancer | Research

The vasculogenic mimicry related signature predicts the prognosis and immunotherapy response in renal clear cell carcinoma

Authors: Yuming Gu, Qinqin Huang, Yun Wang, Haixia Wang, Zhenhua Xiang, Yu Xu, Xin Wang, Weiguo Liu, Aiju Wang

Published in: BMC Cancer | Issue 1/2024

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Abstract

Background

Clear cell carcinoma of the kidney is a common urological malignancy characterized by poor patient prognosis and treatment outcomes. Modulation of vasculogenic mimicry in tumor cells alters the tumor microenvironment and the influx of tumor-infiltrating lymphocytes, and the combination of its inducers and immune checkpoint inhibitors plays a synergistic role in enhancing antitumor effects.

Methods

We downloaded the data from renal clear cell carcinoma samples and vasculogenic mimicry-related genes to establish a new vasculogenic mimicry-related index (VMRI) using a machine learning approach. Based on VMRI, patients with renal clear cell carcinoma were divided into high VMRI and low VMRI groups, and patients’ prognosis, clinical features, tumor immune microenvironment, chemotherapeutic response, and immunotherapeutic response were systematically analyzed. Finally, the function of CDH5 was explored in renal clear cell carcinoma cells.

Results

VMRI can be used for prognostic and immunotherapy efficacy prediction in a variety of cancers, which consists of four vasculogenic mimicry-related genes (CDH5, MMP9, MAPK1, and MMP13), is a reliable predictor of survival and grade in patients with clear cell carcinoma of the kidney and has been validated in multiple external datasets. We found that the high VMRI group presented higher levels of immune cell infiltration, which was validated by pathological sections. We performed molecular docking prediction of vasculogenic mimicry core target proteins and identified natural small molecule drugs with the highest affinity for the target protein. Knockdown of CDH5 inhibited the proliferation and migration of renal clear cell carcinoma.

Conclusions

The VMRI identified in this study allows for accurate prognosis assessment of patients with renal clear cell carcinoma and identification of patient populations that will benefit from immunotherapy, providing valuable insights for future precision treatment of patients with renal clear cell carcinoma.
Appendix
Available only for authorised users
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Metadata
Title
The vasculogenic mimicry related signature predicts the prognosis and immunotherapy response in renal clear cell carcinoma
Authors
Yuming Gu
Qinqin Huang
Yun Wang
Haixia Wang
Zhenhua Xiang
Yu Xu
Xin Wang
Weiguo Liu
Aiju Wang
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-024-12107-x

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