CD44 on cancer stem cell is a potential immunological and prognostic pan-cancer biomarker

作者：Yajuan Zhu, Siying Li, Shan-Shan Yang, Yang Du, Zhuoyuan Zhang, Jiyan Liu · 发表于：Cancer Cell International · 年份：2025 · DOI：10.1186/s12935-025-03748-4 · 被引用次数：15 · 研究领域：Cancer Cells and Metastasis、Cancer Immunotherapy and Biomarkers、Immune cells in cancer

BACKGROUND: CD44, a widely recognized cancer stem cell marker, displayed a vital participation in the cancer immune invasion and may related with the response to the immunotherapy. However, the role of CD44 in cancer immunology is not well defined. Therefore, we intended to explore its prognostic value and potential immunological functions across 33 human cancer types. METHODS: Based on the data of patients from The Cancer Genome Atlas (TCGA), Sangerbox was used to analyze the correlations between CD44 expression and tumor-infiltrated immune cells, immune checkpoints, neoantigens, microsatellite instability (MSI), and tumor mutational burden (TMB) in human cancers. A mouse model xenografted with shRNA-CD44 MC38 was established. RESULTS: The elevated CD44 was associated with tumor stage and prognosis in several different cancers. GSEA results showed that upregulated CD44 involved in cancer stem cell associated process, antigen processing and presentation, and immune cells proliferation and activation. CD44 plays an essential role in the tumor immune regulation and immune checkpoints inhibitor response. The correlation of CD44 gene expression and infiltration levels of immune cells varied across different cancer types. Notably, the upregulation of CD44 expression is positively correlated with regulatory CD4 T cells, macrophages M1 and M2 in several analyzed cancers. Furthermore, we verified the effect of CD44 on tumor growth and immune microenvironment in mouse xenografted with...