Loss of MMP-27 Predicts Mandibular Bone Invasion in Oral Squamous Cell Carcinoma
Invasion of the mandibular bone is frequent in oral squamous cell carcinoma (OSCC), which often results in extensive ablative and reconstructive procedures for the patient. The purpose of this single-center, retrospective study was to identify and evaluate potential biomarkers and risk factors for b...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-08-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/14/16/4044 |
| _version_ | 1797432364849168384 |
|---|---|
| author | Jonas Eichberger Florian Weber Gerrit Spanier Michael Gerken Stephan Schreml Daniela Schulz Mathias Fiedler Nils Ludwig Richard Josef Bauer Torsten Eugen Reichert Tobias Ettl |
| author_facet | Jonas Eichberger Florian Weber Gerrit Spanier Michael Gerken Stephan Schreml Daniela Schulz Mathias Fiedler Nils Ludwig Richard Josef Bauer Torsten Eugen Reichert Tobias Ettl |
| author_sort | Jonas Eichberger |
| collection | DOAJ |
| description | Invasion of the mandibular bone is frequent in oral squamous cell carcinoma (OSCC), which often results in extensive ablative and reconstructive procedures for the patient. The purpose of this single-center, retrospective study was to identify and evaluate potential biomarkers and risk factors for bone invasion in OSCC. Initially, <i>in silico</i> gene expression analysis was performed for different HNSCC tumor T-stages to find factors associated with invasive (T4a) tumor growth. Afterwards, the protein expression of bone-metabolizing MMP-27, TNFRSF11B (Osteoprotegerin, OPG), and TNFSF11 (RANKL) was investigated via Tissue Microarrays (TMAs) for their impact on mandibular bone invasion. TMAs were assembled from the bone–tumor interface of primary OSCCs of the floor of the mouth and gingiva from 119 patients. Sixty-four carcinomas with patho-histological jaw invasion (pT4a) were compared to 55 carcinomas growing along the mandible without invasion (pT2, pT3). Tissue samples were additionally evaluated for patterns of invasion using the WPOI grading system. Statistical analysis of <i>in silico</i> data revealed decreased MMP-27 mRNA expression to be strongly associated with the pT4a-stage in OSCC, indicating invasive tumor growth with infiltration of adjacent anatomical structures. Our own clinico-pathological data on OSCCs presented a significant decrease of MMP-27 in tumors invading the nearby mandible (pT4a), compared to pT2 and pT3 tumors without bone invasion. Loss of MMP27 evolved as the strongest predictor of mandibular bone invasion in binary logistic regression analysis. To our knowledge, this is the first study investigating the role of MMP-27 expression in OSCC and demonstrating the importance of the loss of MMP-27 in mandibular bone invasion. |
| first_indexed | 2024-03-09T09:59:27Z |
| format | Article |
| id | doaj.art-647dcf27f65f40d0b75afe0394fd1738 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T09:59:27Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-647dcf27f65f40d0b75afe0394fd17382023-12-01T23:32:35ZengMDPI AGCancers2072-66942022-08-011416404410.3390/cancers14164044Loss of MMP-27 Predicts Mandibular Bone Invasion in Oral Squamous Cell CarcinomaJonas Eichberger0Florian Weber1Gerrit Spanier2Michael Gerken3Stephan Schreml4Daniela Schulz5Mathias Fiedler6Nils Ludwig7Richard Josef Bauer8Torsten Eugen Reichert9Tobias Ettl10Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, 93053 Regensburg, GermanyInstitute of Pathology, University of Regensburg, 93053 Regensburg, GermanyDepartment of Oral and Maxillofacial Surgery, University Hospital Regensburg, 93053 Regensburg, GermanyTumor Center Regensburg, Institute for Quality Assurance and Health Services Research, University of Regensburg, 93053 Regensburg, GermanyDepartment of Dermatology, University Hospital Regensburg, 93053 Regensburg, GermanyDepartment of Oral and Maxillofacial Surgery and Center for Medical Biotechnology, University Hospital Regensburg, 93053 Regensburg, GermanyDepartment of Oral and Maxillofacial Surgery, University Hospital Regensburg, 93053 Regensburg, GermanyDepartment of Oral and Maxillofacial Surgery, University Hospital Regensburg, 93053 Regensburg, GermanyDepartment of Oral and Maxillofacial Surgery and Center for Medical Biotechnology, University Hospital Regensburg, 93053 Regensburg, GermanyDepartment of Oral and Maxillofacial Surgery, University Hospital Regensburg, 93053 Regensburg, GermanyDepartment of Oral and Maxillofacial Surgery, University Hospital Regensburg, 93053 Regensburg, GermanyInvasion of the mandibular bone is frequent in oral squamous cell carcinoma (OSCC), which often results in extensive ablative and reconstructive procedures for the patient. The purpose of this single-center, retrospective study was to identify and evaluate potential biomarkers and risk factors for bone invasion in OSCC. Initially, <i>in silico</i> gene expression analysis was performed for different HNSCC tumor T-stages to find factors associated with invasive (T4a) tumor growth. Afterwards, the protein expression of bone-metabolizing MMP-27, TNFRSF11B (Osteoprotegerin, OPG), and TNFSF11 (RANKL) was investigated via Tissue Microarrays (TMAs) for their impact on mandibular bone invasion. TMAs were assembled from the bone–tumor interface of primary OSCCs of the floor of the mouth and gingiva from 119 patients. Sixty-four carcinomas with patho-histological jaw invasion (pT4a) were compared to 55 carcinomas growing along the mandible without invasion (pT2, pT3). Tissue samples were additionally evaluated for patterns of invasion using the WPOI grading system. Statistical analysis of <i>in silico</i> data revealed decreased MMP-27 mRNA expression to be strongly associated with the pT4a-stage in OSCC, indicating invasive tumor growth with infiltration of adjacent anatomical structures. Our own clinico-pathological data on OSCCs presented a significant decrease of MMP-27 in tumors invading the nearby mandible (pT4a), compared to pT2 and pT3 tumors without bone invasion. Loss of MMP27 evolved as the strongest predictor of mandibular bone invasion in binary logistic regression analysis. To our knowledge, this is the first study investigating the role of MMP-27 expression in OSCC and demonstrating the importance of the loss of MMP-27 in mandibular bone invasion.https://www.mdpi.com/2072-6694/14/16/4044oral squamous cell carcinomaOSCCMMP-27OPGRANKLmandibular bone invasion |
| spellingShingle | Jonas Eichberger Florian Weber Gerrit Spanier Michael Gerken Stephan Schreml Daniela Schulz Mathias Fiedler Nils Ludwig Richard Josef Bauer Torsten Eugen Reichert Tobias Ettl Loss of MMP-27 Predicts Mandibular Bone Invasion in Oral Squamous Cell Carcinoma Cancers oral squamous cell carcinoma OSCC MMP-27 OPG RANKL mandibular bone invasion |
| title | Loss of MMP-27 Predicts Mandibular Bone Invasion in Oral Squamous Cell Carcinoma |
| title_full | Loss of MMP-27 Predicts Mandibular Bone Invasion in Oral Squamous Cell Carcinoma |
| title_fullStr | Loss of MMP-27 Predicts Mandibular Bone Invasion in Oral Squamous Cell Carcinoma |
| title_full_unstemmed | Loss of MMP-27 Predicts Mandibular Bone Invasion in Oral Squamous Cell Carcinoma |
| title_short | Loss of MMP-27 Predicts Mandibular Bone Invasion in Oral Squamous Cell Carcinoma |
| title_sort | loss of mmp 27 predicts mandibular bone invasion in oral squamous cell carcinoma |
| topic | oral squamous cell carcinoma OSCC MMP-27 OPG RANKL mandibular bone invasion |
| url | https://www.mdpi.com/2072-6694/14/16/4044 |
| work_keys_str_mv | AT jonaseichberger lossofmmp27predictsmandibularboneinvasioninoralsquamouscellcarcinoma AT florianweber lossofmmp27predictsmandibularboneinvasioninoralsquamouscellcarcinoma AT gerritspanier lossofmmp27predictsmandibularboneinvasioninoralsquamouscellcarcinoma AT michaelgerken lossofmmp27predictsmandibularboneinvasioninoralsquamouscellcarcinoma AT stephanschreml lossofmmp27predictsmandibularboneinvasioninoralsquamouscellcarcinoma AT danielaschulz lossofmmp27predictsmandibularboneinvasioninoralsquamouscellcarcinoma AT mathiasfiedler lossofmmp27predictsmandibularboneinvasioninoralsquamouscellcarcinoma AT nilsludwig lossofmmp27predictsmandibularboneinvasioninoralsquamouscellcarcinoma AT richardjosefbauer lossofmmp27predictsmandibularboneinvasioninoralsquamouscellcarcinoma AT torsteneugenreichert lossofmmp27predictsmandibularboneinvasioninoralsquamouscellcarcinoma AT tobiasettl lossofmmp27predictsmandibularboneinvasioninoralsquamouscellcarcinoma |