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

Background CD44, a widespread 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 the prognostic value and the potential immunological functions in 33 human cancer types. Methods Based on the data of patients from The Cancer Genome Atlas (TCGA)and Genotype-Tissue Expression (GTEx) databases, Sangerbox was used to analyze the correlations between CD44 expression and tumor-infiltrated immune cells, immune checkpoints, tumor mutational burden (TMB), microsatellite instability (MSI), and neoantigens in human cancers. Results We found that elevated CD44 is associated with tumor stage and prognosis in different cancers. GSEA results showed that upregulated CD44 involved in cancer stem cell associated process, antigen processing and presentation, and immune response, including immune cell proliferation and activation. Furthermore, CD44 plays an essential role in the tumor microenvironment and participates in immune regulation. The correlation of CD44 gene expression and infiltration levels of most immune cells differed according to the caner types. Notably, the upregulation of CD44 expression is correlated notably positively with Treg, macrophages M1 and M2 in most analyzed cancers, especially in testicular germ cell tumor. Furthermore, we further verified the effect of CD44 on tumor growth and immune microenvironment in mouse xenografted with shRNA-CD44 MC38. Moreover, DNA methylation existed in CD44 expression and associated with dysfunctional T-cell phenotypes via different mechanisms, thus resulting in tissue-dependent prognoses. Conclusion CD44 may serve as a potential prognostic and immunological biomarker in various malignant tumors. Moreover, CD44 could be a novel target for tumor immunotherapy.