Department of Traditional Chinese medicine, School of Clinical Medicine, Affiliated Hospital of Weifang Medical University, Weifang Medical University, Weifang, Shandong Province, 261042, China.
Weifang Medical University, Weifang, Shandong Province, 261042, China.
BMC Cancer. 2024 Apr 5;24(1):420. doi: 10.1186/s12885-024-12107-x.
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.
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.
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.
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.
肾透明细胞癌是一种常见的泌尿系统恶性肿瘤，患者预后和治疗效果较差。肿瘤细胞血管生成拟态的调节改变了肿瘤微环境和肿瘤浸润淋巴细胞的流入，其诱导剂与免疫检查点抑制剂的联合发挥协同作用，增强抗肿瘤效果。
我们从肾透明细胞癌样本和血管生成拟态相关基因中下载数据，使用机器学习方法建立新的血管生成拟态相关指数（VMRI）。基于 VMRI，将肾透明细胞癌患者分为高 VMRI 和低 VMRI 组，系统分析患者的预后、临床特征、肿瘤免疫微环境、化疗反应和免疫治疗反应。最后，探索 CDH5 在肾透明细胞癌细胞中的功能。
VMRI 可以用于多种癌症的预后和免疫治疗疗效预测，由四个血管生成拟态相关基因（CDH5、MMP9、MAPK1 和 MMP13）组成，是肾透明细胞癌患者生存和分级的可靠预测指标，已在多个外部数据集得到验证。我们发现高 VMRI 组的免疫细胞浸润水平更高，这在病理切片中得到了验证。我们对血管生成拟态核心靶蛋白进行了分子对接预测，并确定了与靶蛋白亲和力最高的天然小分子药物。敲低 CDH5 抑制了肾透明细胞癌细胞的增殖和迁移。
本研究中确定的 VMRI 可准确评估肾透明细胞癌患者的预后，并识别出受益于免疫治疗的患者人群，为肾透明细胞癌患者的精准治疗提供了有价值的见解。
