Multiplex single‐cell profiling of putative cancer stem cell markers ALDH1, SOX9, SOX2, CD44, CD133 and CD15 in endometrial cancer
The presence of cancer stem cells is linked to aggressive disease and higher risk of recurrence, and multiple markers have been proposed to detect cancer stem cells. However, a detailed evaluation of the expression patterns and the prognostic value of markers relevant for endometrial cancer is lacki...
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| Format: | Article |
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Wiley
2025-06-01
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| Series: | Molecular Oncology |
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| Online Access: | https://doi.org/10.1002/1878-0261.13815 |
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| author | Hilde E. Lien Marta E. Hjelmeland Hege F. Berg Rose M. Gold Kathrine Woie Lars A. Akslen Ingfrid S. Haldorsen Camilla Krakstad |
| author_facet | Hilde E. Lien Marta E. Hjelmeland Hege F. Berg Rose M. Gold Kathrine Woie Lars A. Akslen Ingfrid S. Haldorsen Camilla Krakstad |
| author_sort | Hilde E. Lien |
| collection | DOAJ |
| description | The presence of cancer stem cells is linked to aggressive disease and higher risk of recurrence, and multiple markers have been proposed to detect cancer stem cells. However, a detailed evaluation of the expression patterns and the prognostic value of markers relevant for endometrial cancer is lacking. As organoid models are suggested to be enriched in cancer stem cells, such models may prove valuable to define tissue‐specific cancer stem cells. To address this, imaging mass cytometry and multiplex single‐cell analyses were performed on an endometrial cancer patient series including both tumor biopsies and corresponding patient‐derived organoids. An antibody panel focused on cancer stem cell markers was used to identify cancer stem cell phenotypes. Over 70% of epithelial cells in the tumor biopsies expressed at least one putative cancer stem cell marker. We identified distinct cancer cell phenotypes with heterogeneous expression within individual patients and between patient samples. Few differences in the distribution of cancer cell phenotypes were observed between tumor biopsies and corresponding organoids. Cells expressing aldehyde dehydrogenase 1 (ALDH1) were more prevalent in high‐grade tumors, while expression of CD44 was more prevalent in grade 1 tumors. Spatial analysis revealed significantly less interaction between ALDH1‐ and CD44‐expressing cells. Gene expression data was used to further investigate selected markers. CD44 gene expression was associated with a favorable prognosis and was further validated using immunohistochemistry. High expression of CD44 was significantly associated with better survival. The general high expression of proposed stem cell markers may indicate alternative roles for these in endometrial cancer. |
| format | Article |
| id | doaj-art-eab5a6dce1bf4e19b549225ff03bf3b0 |
| institution | OA Journals |
| issn | 1574-7891 1878-0261 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj-art-eab5a6dce1bf4e19b549225ff03bf3b02025-08-20T02:22:54ZengWileyMolecular Oncology1574-78911878-02612025-06-011961651166710.1002/1878-0261.13815Multiplex single‐cell profiling of putative cancer stem cell markers ALDH1, SOX9, SOX2, CD44, CD133 and CD15 in endometrial cancerHilde E. Lien0Marta E. Hjelmeland1Hege F. Berg2Rose M. Gold3Kathrine Woie4Lars A. Akslen5Ingfrid S. Haldorsen6Camilla Krakstad7Department of Clinical Science, Centre for Cancer Biomarkers CCBIO University of Bergen NorwayDepartment of Clinical Science, Centre for Cancer Biomarkers CCBIO University of Bergen NorwayDepartment of Clinical Science, Centre for Cancer Biomarkers CCBIO University of Bergen NorwayDepartment of Clinical Science, Centre for Cancer Biomarkers CCBIO University of Bergen NorwayDepartment of Gynecology and Obstetrics Haukeland University Hospital Bergen NorwayDepartment of Clinical Medicine, Centre for Cancer Biomarkers CCBIO University of Bergen NorwayDepartment of Radiology, Mohn Medical Imaging and Visualization Centre Haukeland University Hospital Bergen NorwayDepartment of Clinical Science, Centre for Cancer Biomarkers CCBIO University of Bergen NorwayThe presence of cancer stem cells is linked to aggressive disease and higher risk of recurrence, and multiple markers have been proposed to detect cancer stem cells. However, a detailed evaluation of the expression patterns and the prognostic value of markers relevant for endometrial cancer is lacking. As organoid models are suggested to be enriched in cancer stem cells, such models may prove valuable to define tissue‐specific cancer stem cells. To address this, imaging mass cytometry and multiplex single‐cell analyses were performed on an endometrial cancer patient series including both tumor biopsies and corresponding patient‐derived organoids. An antibody panel focused on cancer stem cell markers was used to identify cancer stem cell phenotypes. Over 70% of epithelial cells in the tumor biopsies expressed at least one putative cancer stem cell marker. We identified distinct cancer cell phenotypes with heterogeneous expression within individual patients and between patient samples. Few differences in the distribution of cancer cell phenotypes were observed between tumor biopsies and corresponding organoids. Cells expressing aldehyde dehydrogenase 1 (ALDH1) were more prevalent in high‐grade tumors, while expression of CD44 was more prevalent in grade 1 tumors. Spatial analysis revealed significantly less interaction between ALDH1‐ and CD44‐expressing cells. Gene expression data was used to further investigate selected markers. CD44 gene expression was associated with a favorable prognosis and was further validated using immunohistochemistry. High expression of CD44 was significantly associated with better survival. The general high expression of proposed stem cell markers may indicate alternative roles for these in endometrial cancer.https://doi.org/10.1002/1878-0261.13815cancer stem cellsendometrial cancerimaging mass cytometrypatient‐derived organoidssingle celltumor heterogeneity |
| spellingShingle | Hilde E. Lien Marta E. Hjelmeland Hege F. Berg Rose M. Gold Kathrine Woie Lars A. Akslen Ingfrid S. Haldorsen Camilla Krakstad Multiplex single‐cell profiling of putative cancer stem cell markers ALDH1, SOX9, SOX2, CD44, CD133 and CD15 in endometrial cancer Molecular Oncology cancer stem cells endometrial cancer imaging mass cytometry patient‐derived organoids single cell tumor heterogeneity |
| title | Multiplex single‐cell profiling of putative cancer stem cell markers ALDH1, SOX9, SOX2, CD44, CD133 and CD15 in endometrial cancer |
| title_full | Multiplex single‐cell profiling of putative cancer stem cell markers ALDH1, SOX9, SOX2, CD44, CD133 and CD15 in endometrial cancer |
| title_fullStr | Multiplex single‐cell profiling of putative cancer stem cell markers ALDH1, SOX9, SOX2, CD44, CD133 and CD15 in endometrial cancer |
| title_full_unstemmed | Multiplex single‐cell profiling of putative cancer stem cell markers ALDH1, SOX9, SOX2, CD44, CD133 and CD15 in endometrial cancer |
| title_short | Multiplex single‐cell profiling of putative cancer stem cell markers ALDH1, SOX9, SOX2, CD44, CD133 and CD15 in endometrial cancer |
| title_sort | multiplex single cell profiling of putative cancer stem cell markers aldh1 sox9 sox2 cd44 cd133 and cd15 in endometrial cancer |
| topic | cancer stem cells endometrial cancer imaging mass cytometry patient‐derived organoids single cell tumor heterogeneity |
| url | https://doi.org/10.1002/1878-0261.13815 |
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