Clinical Significance of Stem Cell Biomarkers EpCAM, LGR5 and LGR4 mRNA Levels in Lymph Nodes of Colon Cancer Patients
The significance of cancer stem cells (CSCs) in initiation and progression of colon cancer (CC) has been established. In this study, we investigated the utility of measuring mRNA expression levels of CSC markers EpCAM, LGR5 and LGR4 for predicting survival outcome in surgically treated CC patients....
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| Format: | Article |
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/1/403 |
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| author | Manar AbdelMageed Hager Tarek H. Ismail Lina Olsson Gudrun Lindmark Marie-Louise Hammarström Sten Hammarström Basel Sitohy |
| author_facet | Manar AbdelMageed Hager Tarek H. Ismail Lina Olsson Gudrun Lindmark Marie-Louise Hammarström Sten Hammarström Basel Sitohy |
| author_sort | Manar AbdelMageed |
| collection | DOAJ |
| description | The significance of cancer stem cells (CSCs) in initiation and progression of colon cancer (CC) has been established. In this study, we investigated the utility of measuring mRNA expression levels of CSC markers EpCAM, LGR5 and LGR4 for predicting survival outcome in surgically treated CC patients. Expression levels were determined in 5 CC cell lines, 66 primary CC tumors and 382 regional lymph nodes of 121 CC patients. Prognostic relevance was determined using Kaplan-Meier survival and Cox regression analyses. CC patients with lymph nodes expressing high levels of EpCAM, LGR5 or LGR4 (higher than a clinical cutoff of 0.07, 0.06 and 2.558 mRNA copies/18S rRNA unit, respectively) had a decreased mean survival time of 32 months for EpCAM and 42 months for both LGR5 and LGR4 at a 12-year follow-up (<i>p</i> = 0.022, <i>p</i> = 0.005 and <i>p</i> = 0.011, respectively). Additional patients at risk for recurrence were detected when LGR5 was combined with the biomarkers CXCL17 or CEA plus CXCL16. In conclusion, the study underscores LGR5 as a particularly useful prognostic biomarker and illustrates the strength of combining biomarkers detecting different subpopulations of cancer cells and/or cells in the tumor microenvironment for predicting recurrence. |
| first_indexed | 2024-03-10T03:38:29Z |
| format | Article |
| id | doaj.art-4595bbded33a4b129a5da325a389d721 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:38:29Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4595bbded33a4b129a5da325a389d7212023-11-23T11:39:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0123140310.3390/ijms23010403Clinical Significance of Stem Cell Biomarkers EpCAM, LGR5 and LGR4 mRNA Levels in Lymph Nodes of Colon Cancer PatientsManar AbdelMageed0Hager Tarek H. Ismail1Lina Olsson2Gudrun Lindmark3Marie-Louise Hammarström4Sten Hammarström5Basel Sitohy6Department of Clinical Microbiology, Infection and Immunology, Umeå University, SE-90185 Umeå, SwedenDepartment of Clinical Microbiology, Infection and Immunology, Umeå University, SE-90185 Umeå, SwedenDepartment of Clinical Microbiology, Infection and Immunology, Umeå University, SE-90185 Umeå, SwedenInstitution of Clinical Sciences, Lund University, SE-25187 Helsingborg, SwedenDepartment of Clinical Microbiology, Infection and Immunology, Umeå University, SE-90185 Umeå, SwedenDepartment of Clinical Microbiology, Infection and Immunology, Umeå University, SE-90185 Umeå, SwedenDepartment of Clinical Microbiology, Infection and Immunology, Umeå University, SE-90185 Umeå, SwedenThe significance of cancer stem cells (CSCs) in initiation and progression of colon cancer (CC) has been established. In this study, we investigated the utility of measuring mRNA expression levels of CSC markers EpCAM, LGR5 and LGR4 for predicting survival outcome in surgically treated CC patients. Expression levels were determined in 5 CC cell lines, 66 primary CC tumors and 382 regional lymph nodes of 121 CC patients. Prognostic relevance was determined using Kaplan-Meier survival and Cox regression analyses. CC patients with lymph nodes expressing high levels of EpCAM, LGR5 or LGR4 (higher than a clinical cutoff of 0.07, 0.06 and 2.558 mRNA copies/18S rRNA unit, respectively) had a decreased mean survival time of 32 months for EpCAM and 42 months for both LGR5 and LGR4 at a 12-year follow-up (<i>p</i> = 0.022, <i>p</i> = 0.005 and <i>p</i> = 0.011, respectively). Additional patients at risk for recurrence were detected when LGR5 was combined with the biomarkers CXCL17 or CEA plus CXCL16. In conclusion, the study underscores LGR5 as a particularly useful prognostic biomarker and illustrates the strength of combining biomarkers detecting different subpopulations of cancer cells and/or cells in the tumor microenvironment for predicting recurrence.https://www.mdpi.com/1422-0067/23/1/403colon cancerEpCAMLGR5LGR4CEACXCL17 |
| spellingShingle | Manar AbdelMageed Hager Tarek H. Ismail Lina Olsson Gudrun Lindmark Marie-Louise Hammarström Sten Hammarström Basel Sitohy Clinical Significance of Stem Cell Biomarkers EpCAM, LGR5 and LGR4 mRNA Levels in Lymph Nodes of Colon Cancer Patients International Journal of Molecular Sciences colon cancer EpCAM LGR5 LGR4 CEA CXCL17 |
| title | Clinical Significance of Stem Cell Biomarkers EpCAM, LGR5 and LGR4 mRNA Levels in Lymph Nodes of Colon Cancer Patients |
| title_full | Clinical Significance of Stem Cell Biomarkers EpCAM, LGR5 and LGR4 mRNA Levels in Lymph Nodes of Colon Cancer Patients |
| title_fullStr | Clinical Significance of Stem Cell Biomarkers EpCAM, LGR5 and LGR4 mRNA Levels in Lymph Nodes of Colon Cancer Patients |
| title_full_unstemmed | Clinical Significance of Stem Cell Biomarkers EpCAM, LGR5 and LGR4 mRNA Levels in Lymph Nodes of Colon Cancer Patients |
| title_short | Clinical Significance of Stem Cell Biomarkers EpCAM, LGR5 and LGR4 mRNA Levels in Lymph Nodes of Colon Cancer Patients |
| title_sort | clinical significance of stem cell biomarkers epcam lgr5 and lgr4 mrna levels in lymph nodes of colon cancer patients |
| topic | colon cancer EpCAM LGR5 LGR4 CEA CXCL17 |
| url | https://www.mdpi.com/1422-0067/23/1/403 |
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