CD44 on cancer stem cell is a potential immunological and prognostic pan-cancer biomarker
Abstract 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 progn...
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| Format: | Article |
| Language: | English |
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BMC
2025-04-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-025-03748-4 |
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| author | Ya-Juan Zhu Si-Ying Li Shan-Shan Yang Yang Du Zhuo-Yuan Zhang Ji-Yan Liu |
| author_facet | Ya-Juan Zhu Si-Ying Li Shan-Shan Yang Yang Du Zhuo-Yuan Zhang Ji-Yan Liu |
| author_sort | Ya-Juan Zhu |
| collection | DOAJ |
| description | Abstract 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 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 is both a cancer stem cell marker and a potential prognostic and immunological biomarker in various malignant tumors. Moreover, CD44 could be a novel target for immune-based therapy. |
| format | Article |
| id | doaj-art-3519e4ea913c447e8d6ab6d0c8fc22ab |
| institution | OA Journals |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-3519e4ea913c447e8d6ab6d0c8fc22ab2025-08-20T02:17:05ZengBMCCancer Cell International1475-28672025-04-0125111410.1186/s12935-025-03748-4CD44 on cancer stem cell is a potential immunological and prognostic pan-cancer biomarkerYa-Juan Zhu0Si-Ying Li1Shan-Shan Yang2Yang Du3Zhuo-Yuan Zhang4Ji-Yan Liu5Department of Biotherapy, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Liver Surgery, Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityMolecular Medicine Research Center, West China Hospital, Sichuan UniversityDepartment of Biotherapy, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Head and Neck Cancer Surgery, West China School of Stomatology, Sichuan UniversityDepartment of Biotherapy, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityAbstract 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 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 is both a cancer stem cell marker and a potential prognostic and immunological biomarker in various malignant tumors. Moreover, CD44 could be a novel target for immune-based therapy.https://doi.org/10.1186/s12935-025-03748-4CD44Infiltrated immune cellsImmune checkpointsCancer prognosis |
| spellingShingle | Ya-Juan Zhu Si-Ying Li Shan-Shan Yang Yang Du Zhuo-Yuan Zhang Ji-Yan Liu CD44 on cancer stem cell is a potential immunological and prognostic pan-cancer biomarker Cancer Cell International CD44 Infiltrated immune cells Immune checkpoints Cancer prognosis |
| title | CD44 on cancer stem cell is a potential immunological and prognostic pan-cancer biomarker |
| title_full | CD44 on cancer stem cell is a potential immunological and prognostic pan-cancer biomarker |
| title_fullStr | CD44 on cancer stem cell is a potential immunological and prognostic pan-cancer biomarker |
| title_full_unstemmed | CD44 on cancer stem cell is a potential immunological and prognostic pan-cancer biomarker |
| title_short | CD44 on cancer stem cell is a potential immunological and prognostic pan-cancer biomarker |
| title_sort | cd44 on cancer stem cell is a potential immunological and prognostic pan cancer biomarker |
| topic | CD44 Infiltrated immune cells Immune checkpoints Cancer prognosis |
| url | https://doi.org/10.1186/s12935-025-03748-4 |
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