Detection of lymph node metastasis in colon cancer by ectopically expressed fibroblast markers FOXQ1 and THBS2
IntroductionApproximately 25% of colon cancer (CC) patients having curative surgery will relapse. Therefore, it is crucial to identify patients with increased recurrence risk to offer them adjuvant chemotherapy. Three markers with prominent expression in fibroblasts: forkhead box Q1 (FOXQ1), matrix...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1297324/full |
| _version_ | 1797390277623676928 |
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| author | Haytham Ali Haytham Ali Haytham Ali Manar AbdelMageed Manar AbdelMageed Manar AbdelMageed Lina Olsson Gudrun Lindmark Marie-Louise Hammarström Sten Hammarström Basel Sitohy Basel Sitohy |
| author_facet | Haytham Ali Haytham Ali Haytham Ali Manar AbdelMageed Manar AbdelMageed Manar AbdelMageed Lina Olsson Gudrun Lindmark Marie-Louise Hammarström Sten Hammarström Basel Sitohy Basel Sitohy |
| author_sort | Haytham Ali |
| collection | DOAJ |
| description | IntroductionApproximately 25% of colon cancer (CC) patients having curative surgery will relapse. Therefore, it is crucial to identify patients with increased recurrence risk to offer them adjuvant chemotherapy. Three markers with prominent expression in fibroblasts: forkhead box Q1 (FOXQ1), matrix metalloproteinase-11 (MMP11), and thrombospondin-2 (THBS2), and the fibroblast expressed chemokine CXCL12 were selected for studies because of the critical role of fibroblasts in the microenvironment of the tumor.MethodsThe expression levels of the biomarkers were assessed in primary CC tumors, lymph nodes of CC patients and controls, and CC cell lines at mRNA and protein levels by real-time qRT-PCR and immunohistochemistry, respectively.ResultsFOXQ1, MMP11, and THBS2 mRNAs were expressed at significantly higher levels in primary tumors compared to normal colon (P=0.002, P<0.0001, and P<0.0001, respectively). In contrast, CXCL12 mRNA levels were higher in normal colon tissue. FOXQ1, MMP11, and THBS2 levels were also expressed at significantly higher levels in metastasis-positive lymph nodes compared to both metastasis-negative- and control nodes (P<0.0001/P=0.002, P<0.0001/P<0.0001, and P<0.0001/P<0.0001, respectively). Immuno-morphometry revealed that 30–40% of the tumor cells expressed FOXQ1, MMP11, and THBS2. FOXQ1 and THBS2 were barely detected in normal colon epithelium (P<0.0001), while MMP11 was expressed in normal colon epithelium at high levels.DiscussionWe conclude that CC tumor cells show ectopic expression of FOXQ1 and THBS2 possibly making these tumor cells independent of fibroblast cell support. The high expression levels of these two biomarkers in metastatic lymph nodes suggest that they are potential indicators of patients at risk for recurrence. |
| first_indexed | 2024-03-08T23:09:23Z |
| format | Article |
| id | doaj.art-56d4ebe012504fed8377f8f5dc7c7687 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-08T23:09:23Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-56d4ebe012504fed8377f8f5dc7c76872023-12-15T07:58:00ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-12-011310.3389/fonc.2023.12973241297324Detection of lymph node metastasis in colon cancer by ectopically expressed fibroblast markers FOXQ1 and THBS2Haytham Ali0Haytham Ali1Haytham Ali2Manar AbdelMageed3Manar AbdelMageed4Manar AbdelMageed5Lina Olsson6Gudrun Lindmark7Marie-Louise Hammarström8Sten Hammarström9Basel Sitohy10Basel Sitohy11Department of Clinical Microbiology, Umeå University, Umeå, SwedenDepartment of Radiation Sciences, Oncology, Umeå University, Umeå, SwedenDepartment of Animal and Veterinary Sciences, College of Agricultural and Marine Sciences, Sultan Qaboos University, Muscat, OmanDepartment of Clinical Microbiology, Umeå University, Umeå, SwedenDepartment of Radiation Sciences, Oncology, Umeå University, Umeå, SwedenDepartment of Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, EgyptDepartment of Clinical Microbiology, Umeå University, Umeå, SwedenInstitution of Clinical Sciences, Lund University, Lund, SwedenDepartment of Clinical Microbiology, Umeå University, Umeå, SwedenDepartment of Clinical Microbiology, Umeå University, Umeå, SwedenDepartment of Clinical Microbiology, Umeå University, Umeå, SwedenDepartment of Radiation Sciences, Oncology, Umeå University, Umeå, SwedenIntroductionApproximately 25% of colon cancer (CC) patients having curative surgery will relapse. Therefore, it is crucial to identify patients with increased recurrence risk to offer them adjuvant chemotherapy. Three markers with prominent expression in fibroblasts: forkhead box Q1 (FOXQ1), matrix metalloproteinase-11 (MMP11), and thrombospondin-2 (THBS2), and the fibroblast expressed chemokine CXCL12 were selected for studies because of the critical role of fibroblasts in the microenvironment of the tumor.MethodsThe expression levels of the biomarkers were assessed in primary CC tumors, lymph nodes of CC patients and controls, and CC cell lines at mRNA and protein levels by real-time qRT-PCR and immunohistochemistry, respectively.ResultsFOXQ1, MMP11, and THBS2 mRNAs were expressed at significantly higher levels in primary tumors compared to normal colon (P=0.002, P<0.0001, and P<0.0001, respectively). In contrast, CXCL12 mRNA levels were higher in normal colon tissue. FOXQ1, MMP11, and THBS2 levels were also expressed at significantly higher levels in metastasis-positive lymph nodes compared to both metastasis-negative- and control nodes (P<0.0001/P=0.002, P<0.0001/P<0.0001, and P<0.0001/P<0.0001, respectively). Immuno-morphometry revealed that 30–40% of the tumor cells expressed FOXQ1, MMP11, and THBS2. FOXQ1 and THBS2 were barely detected in normal colon epithelium (P<0.0001), while MMP11 was expressed in normal colon epithelium at high levels.DiscussionWe conclude that CC tumor cells show ectopic expression of FOXQ1 and THBS2 possibly making these tumor cells independent of fibroblast cell support. The high expression levels of these two biomarkers in metastatic lymph nodes suggest that they are potential indicators of patients at risk for recurrence.https://www.frontiersin.org/articles/10.3389/fonc.2023.1297324/fullTHBS2FOXQ1MMP11CXCL12colon cancerfibroblasts |
| spellingShingle | Haytham Ali Haytham Ali Haytham Ali Manar AbdelMageed Manar AbdelMageed Manar AbdelMageed Lina Olsson Gudrun Lindmark Marie-Louise Hammarström Sten Hammarström Basel Sitohy Basel Sitohy Detection of lymph node metastasis in colon cancer by ectopically expressed fibroblast markers FOXQ1 and THBS2 Frontiers in Oncology THBS2 FOXQ1 MMP11 CXCL12 colon cancer fibroblasts |
| title | Detection of lymph node metastasis in colon cancer by ectopically expressed fibroblast markers FOXQ1 and THBS2 |
| title_full | Detection of lymph node metastasis in colon cancer by ectopically expressed fibroblast markers FOXQ1 and THBS2 |
| title_fullStr | Detection of lymph node metastasis in colon cancer by ectopically expressed fibroblast markers FOXQ1 and THBS2 |
| title_full_unstemmed | Detection of lymph node metastasis in colon cancer by ectopically expressed fibroblast markers FOXQ1 and THBS2 |
| title_short | Detection of lymph node metastasis in colon cancer by ectopically expressed fibroblast markers FOXQ1 and THBS2 |
| title_sort | detection of lymph node metastasis in colon cancer by ectopically expressed fibroblast markers foxq1 and thbs2 |
| topic | THBS2 FOXQ1 MMP11 CXCL12 colon cancer fibroblasts |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1297324/full |
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