Loss of MMP-27 Predicts Mandibular Bone Invasion in Oral Squamous Cell Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. mRNA Expression Analysis Using the cBioPortal Database
2.2. Patients
2.3. Assessment of Tumor Invasion
2.4. Immunohistochemical Sample Preparation and Staining Protocol
2.5. IHC Staining Assessment
2.6. Statistical Analysis
3. Results
3.1. In Silico Data Analysis via the cBioPortal Database
3.2. Immunohistochemical Expression of MMP-27, RANKL and OPG in OSCC Tissue and Comparison to Clinico-Pathological Parameters
Patient Characteristics
3.3. Worst Pattern of Invasion Score and Relationship to Patient Data
3.4. Immunohistochemical Staining of MMP-27, RANKL and OPG and Association with Clinico-Pathological Parameters, Particularly Bone Invasion
3.4.1. MMP-27 Expression
3.4.2. RANKL and OPG Expression
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameter | MMP-27 (N = 119) | RANKL (N = 119) | OPG (N = 85) | |||||||
---|---|---|---|---|---|---|---|---|---|---|
N | Low | High | p-Value | Negative | Positive | p-Value | Low | High | p-Value | |
Age | ||||||||||
(Mean: 62.2 years; 38–89 years) | ||||||||||
>62 years | 51 (42.9%) | 23 (45.1%) | 28 (54.9%) | 33 (64.7%) | 18 (35.3%) | 19 (46.3%) | 22 (53.7%) | |||
≤62 years | 68 (57.1%) | 34 (50.0%) | 34 (50.0%) | 0.711 | 40 (58.8%) | 28 (42.2%) | 0.571 | 32 (72.7%) | 12 (27.3%) | 0.016 |
Sex | ||||||||||
male | 95 (79.8%) | 44 (46.3%) | 51 (53.7%) | 58 (61.0%) | 37 (39.0%) | 42 (62.7%) | 25 (37.3%) | |||
female | 24 (20.2%) | 13 (54.2%) | 11 (53.0%) | 0.504 | 15 (62.5%) | 9 (37.5%) | 1.000 | 9 (50.0%) | 9 (50.0%) | 0.418 |
Anatomic Site | ||||||||||
Gingiva | 53 (44.5%) | 26 (49.1%) | 27 (50.9%) | 30 (56.6%) | 23 (43.4%) | 24 (57.1%) | 18 (42.9%) | |||
Floor of mouth | 66 (55.5%) | 31 (47.0%) | 35 (53.0%) | 0.855 | 43 (66.2%) | 23 (33.8%) | 0.352 | 27 (62.8%) | 16 (37.2%) | 0.661 |
Tobacco use | ||||||||||
Yes | 95 (73.9%) | 46 (48.4%) | 49 (51.6%) | 58 (61.0%) | 37 (39.0%) | 44 (66.7%) | 22 (33.3%) | |||
No | 24 (20.2%) | 11 (45.8%) | 13 (54.2%) | 1.000 | 15 (62.5%) | 9 (37.5%) | 1.000 | 7 (36.8%) | 12 (63.2%) | 0.032 |
Alcohol use | ||||||||||
Yes | 88 (73.9%) | 43 (48.9%) | 45 (51.1%) | 54 (61.4%) | 34 (38.6%) | 38 (63.3%) | 22 (36.7%) | |||
No | 31 (26.1%) | 14 (45.2%) | 17 (54.8%) | 0.835 | 19 (61.3%) | 12 (38.7%) | 0.655 | 13 (52.0%) | 12 (48.0%) | 0.467 |
T-stage | ||||||||||
pT2 + pT3 | 55 (46.6%) | 20 (36.4%) | 35 (63.6%) | 36 (65.5%) | 19 (34.5%) | 17 (48.6%) | 18 (51.4%) | |||
pT4a (mandibular bone invasion) | 64 (53.8%) | 37 (57.8%) | 27 (42.2%) | 0.027 | 37 (57.8%) | 27 (42.2%) | 0.452 | 34 (68.0%) | 16 (32.0%) | 0.115 |
N-stage | ||||||||||
N0 | 57 (47.9%) | 27 (47.4%) | 30 (52.6%) | 30 (52.6%) | 27 (47.4%) | 23 (54.8%) | 19 (45.2%) | |||
N+ | 62 (52.1%) | 30 (48.4%) | 32 (51.6%) | 1.000 | 43 (69.4%) | 19 (30.6%) | 0.089 | 28 (65.1%) | 15 (34.9%) | 0.380 |
UICC-stage | ||||||||||
II + III | 37 (28.8%) | 18 (48.6%) | 19 (51.4%) | 21 (56.8%) | 16 (43.2%) | 14 (53.8%) | 12 (46.2%) | |||
IV | 82 (72.2%) | 39 (47.6%) | 43 (52.4%) | 1.000 | 52 (63.4%) | 30 (36.6%) | 0.544 | 37 (62.7%) | 22 (37.3%) | 0.478 |
Grade | ||||||||||
G1 + G2 | 101 (84.9%) | 44 (43.6%) | 57 (56.4%) | 64 (63.4%) | 37 (36.6%) | 41 (56.9%) | 31 (43.1%) | |||
G3 | 18 (15.1%) | 13 (72.2%) | 5 (27.8%) | 0.039 | 9 (50.0%) | 9 (50.0%) | 0.304 | 10 (76.9%) | 3 (23.1%) | 0.277 |
Tumor Recurrence | ||||||||||
Yes | 36 (30.3%) | 14 (38.9%) | 22 (61.1%) | 19 (52.8%) | 17 (47.2%) | 12 (57.1%) | 9 (42.9%) | |||
No | 83 (69.7%) | 43 (51.8%) | 40 (48.2%) | 0.233 | 53 (63.9%) | 30 (36.1%) | 0.309 | 39 (60.9%) | 25 (29.1%) | 0.801 |
WPOI grade | ||||||||||
Non-aggressive | 61 (51.3%) | 29 (47.5%) | 32 (52.5%) | 30 (49.2%) | 31 (50.8%) | 33 (70.2%) | 14 (29.8%) | |||
Aggressive | 58 (48.7%) | 28 (48.3%) | 30 (51.7%) | 1.000 | 33 (56.9%) | 25 (43.1%) | 0.464 | 18 (47.4%) | 20 (52.6%) | 0.045 |
HL | β | SE | Wald | p | Exp (β) (95% CI) | ||
---|---|---|---|---|---|---|---|
pT2 + pT3 vs. pT4a | 0.221 | High MMP27 | −0.828 | 0.392 | 4.459 | 0.035 | 0.437 (0.203–0.942) |
RANKL | −0.182 | 0.415 | 0.192 | 0.662 | 0.834 (0.370–1.881) | ||
High OPG | 0.349 | 0.427 | 0.670 | 0.413 | 1.418 (0.614–3.274) | ||
WPOI Grade 4-5 | −0.146 | 0.402 | 0.132 | 0.717 | 0.864 (0.393–1.900) | ||
Grade | −0.307 | 0.566 | 0.295 | 0.587 | 0.735 (0.242–2.231) |
MMP-27 | RANKL | OPG | ||
---|---|---|---|---|
MMP-27 | Spearman’s ρ | 1.000 | 0.239 | 0.480 |
p-value | - | 0.009 | <0.001 | |
N | 119 | 119 | 85 | |
RANKL | Spearman’s ρ | 0.239 | 1.000 | 0.381 |
p-value | 0.009 | - | <0.001 | |
N | 119 | 119 | 85 | |
OPG | Spearman’s ρ | 0.480 | 0.381 | 1.000 |
p-value | <0.001 | <0.001 | - | |
N | 85 | 85 | 85 |
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Eichberger, J.; Weber, F.; Spanier, G.; Gerken, M.; Schreml, S.; Schulz, D.; Fiedler, M.; Ludwig, N.; Bauer, R.J.; Reichert, T.E.; et al. Loss of MMP-27 Predicts Mandibular Bone Invasion in Oral Squamous Cell Carcinoma. Cancers 2022, 14, 4044. https://doi.org/10.3390/cancers14164044
Eichberger J, Weber F, Spanier G, Gerken M, Schreml S, Schulz D, Fiedler M, Ludwig N, Bauer RJ, Reichert TE, et al. Loss of MMP-27 Predicts Mandibular Bone Invasion in Oral Squamous Cell Carcinoma. Cancers. 2022; 14(16):4044. https://doi.org/10.3390/cancers14164044
Chicago/Turabian StyleEichberger, Jonas, Florian Weber, Gerrit Spanier, Michael Gerken, Stephan Schreml, Daniela Schulz, Mathias Fiedler, Nils Ludwig, Richard Josef Bauer, Torsten Eugen Reichert, and et al. 2022. "Loss of MMP-27 Predicts Mandibular Bone Invasion in Oral Squamous Cell Carcinoma" Cancers 14, no. 16: 4044. https://doi.org/10.3390/cancers14164044