Matrix Metalloproteinase 9/microRNA-145 Ratio: Bridging Genomic and Immunological Variabilities in Thyroid Cancer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Analysis of Tissues and Blood Specimens of Thyroid Cancer Patients
2.1.1. Study Population
2.1.2. Clinical and Pathological Assessment
2.1.3. Tissue Sample Processing and Histopathological Assessment
2.1.4. Blood Sampling Procedure and Longitudinal Follow-Up
2.1.5. Total RNA/miRNA Extraction
2.1.6. miR-145 Expression Analysis
2.1.7. MMP9 mRNA Expression Analysis
2.1.8. Tissue Microarray (TMA)
2.1.9. Immunofluorescence Analysis and Quantification of Protein Expression Data
2.2. In Silico Data Analysis
2.3. Systematic Review on the Clinical Significance of MMP9 and miR-145
2.4. Statistical Analysis
3. Results
3.1. Analysis of Tissues and Blood Specimens of Thyroid Cancer Patients
3.1.1. Characteristics of the Study Population of Tissue Samples
3.1.2. Diagnostic Performance of MMP9/miR-145 Ratio in Thyroid Tissues
3.1.3. Prognostic Performance of MMP9/miR-145 Ratio
3.1.4. Stratified Analysis
3.1.5. Survival Analysis
3.1.6. Circulatory MMP9/miR-145 Ratio Expression Levels
3.1.7. Clinical Implication of Preoperative MMP9/miR-145 Ratio in PTC Patients
3.1.8. Over a 12–18-Month Post-Operative Duration, a Longitudinal Assessment was Conducted on the Initial Cohort of 86 PTC Patients
3.1.9. Distinctive MMP9 Expression Patterns across Thyroid Tissue Types
3.1.10. Unraveling the Intricate Interplay between MMP9 Expression and Immune Infiltration
3.2. In Silico Data Analysis
3.2.1. Genomic Structure of MMP9
3.2.2. MMP9-miR-145 Interaction
3.2.3. The Link of MMP9 and miR-145 with Immunity in Thyroid Tissues: Insights from Multi-Dataset Analyses
3.3. Systematic Review
3.3.1. Functional Analysis of MMP9 and miR-145
3.3.2. MMP9 and miR-145 Expression in Thyroid Cancer
3.3.3. Associations with Clinicopathological Features
3.3.4. Longitudinal Studies for Prognostication
3.3.5. Impact of MMP9 Inhibition and miR-145 Activation on Thyroid Cancer
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Patient Characteristics | Levels | BRAFV600E Mutation | p-Value | Hashimoto’s Thyroiditis | p-Value | ||
---|---|---|---|---|---|---|---|
Negative | Positive | Negative | Positive | ||||
Total number | 97 | 78 | 149 | 26 | |||
Demographic data | |||||||
Age, years | <55 years | 71 (73.2%) | 48 (61.5%) | 0.11 | 101 (67.8%) | 18 (69.2%) | 0.88 |
≥55 years | 26 (26.8%) | 30 (38.5%) | 48 (32.2%) | 8 (30.8%) | |||
Sex | Female | 60 (61.9%) | 59 (75.6%) | 0.07 | 101 (67.8%) | 18 (69.2%) | 0.88 |
Male | 37 (38.1%) | 19 (24.4%) | 48 (32.2%) | 8 (30.8%) | |||
Obesity | Negative | 6 (6.2%) | 8 (10.3%) | 0.40 | 12 (8.1%) | 2 (7.7%) | 0.95 |
Positive | 91 (93.8%) | 70 (89.7%) | 137 (91.9%) | 24 (92.3%) | |||
Smoking | Negative | 87 (89.7%) | 73 (93.6%) | 0.42 | 136 (91.3%) | 24 (92.3%) | 0.86 |
Positive | 10 (10.3%) | 5 (6.4%) | 13 (8.7%) | 2 (7.7%) | |||
Hepatitis C virus | Negative | 50 (51.5%) | 49 (62.8%) | 0.17 | 81 (54.4%) | 18 (69.2%) | 0.20 |
Positive | 47 (48.5%) | 29 (37.2%) | 68 (45.6%) | 8 (30.8%) | |||
Genomic mutation | |||||||
RAS gene mutation | Negative | 86 (88.7%) | 74 (94.9%) | 0.18 | 141 (94.6%) | 19 (73.1%) | 0.002 |
Positive | 11 (11.3%) | 4 (5.1%) | 8 (5.4%) | 7 (26.9%) | |||
Pathological data | |||||||
Laterality | Unilateral | 64 (0.7%) | 56 (0.7%) | 0.51 | 100 (0.7%) | 20 (0.8%) | 0.37 |
Bilateral | 33 (0.3%) | 22 (0.3%) | 49 (0.3%) | 6 (0.2%) | |||
Focality | Unifocal | 86 (0.9%) | 59 (0.8%) | 0.027 | 121 (0.8%) | 24 (0.9%) | 0.26 |
Multifocal | 11 (0.1%) | 19 (0.2%) | 28 (0.2%) | 2 (0.1%) | |||
T stage | T1a | 21 (21.6%) | 26 (33.3%) | <0.001 | 39 (26.2%) | 8 (30.8%) | 0.75 |
T1b | 17 (17.5%) | 29 (37.2%) | 39 (26.2%) | 7 (26.9%) | |||
T2 | 54 (55.7%) | 16 (20.5%) | 60 (40.3%) | 10 (38.5%) | |||
T3 | 2 (2.1%) | 6 (7.7%) | 8 (5.4%) | 0 (0%) | |||
T4 | 3 (3.1%) | 1 (1.3%) | 3 (2%) | 1 (3.8%) | |||
N stage | N0 | 54 (55.7%) | 47 (60.3%) | 0.64 | 83 (55.7%) | 18 (69.2%) | 0.28 |
N1 | 43 (44.3%) | 31 (39.7%) | 66 (44.3%) | 8 (30.8%) | |||
M stage | M0 | 87 (89.7%) | 58 (74.4%) | 0.009 | 121 (81.2%) | 24 (92.3%) | 0.26 |
M1 | 10 (10.3%) | 20 (25.6%) | 28 (18.8%) | 2 (7.7%) | |||
Pathology stage | Stage I | 69 (71.1%) | 46 (59%) | 0.027 | 95 (63.8%) | 20 (76.9%) | 0.54 |
Stage II | 6 (6.2%) | 8 (10.3%) | 12 (8.1%) | 2 (7.7%) | |||
Stage III | 10 (10.3%) | 2 (2.6%) | 11 (7.4%) | 1 (3.8%) | |||
Stage IVA | 4 (4.1%) | 7 (9%) | 11 (7.4%) | 0 (0%) | |||
Stage IVB | 2 (2.1%) | 1 (1.3%) | 2 (1.3%) | 1 (3.8%) | |||
Stage IVC | 6 (6.2%) | 14 (17.9%) | 18 (12.1%) | 2 (7.7%) | |||
Extrathyroidal extension | Negative | 78 (80.4%) | 59 (75.6%) | 0.47 | 119 (79.9%) | 18 (69.2%) | 0.30 |
Positive | 19 (19.6%) | 19 (24.4%) | 30 (20.1%) | 8 (30.8%) | |||
Perineural invasion | Negative | 94 (96.9%) | 77 (98.7%) | 0.63 | 145 (97.3%) | 26 (100%) | 0.39 |
Positive | 3 (3.1%) | 1 (1.3%) | 4 (2.7%) | 0 (0%) | |||
Extranodal extension | Negative | 94 (96.9%) | 69 (88.5%) | 0.036 | 138 (92.6%) | 25 (96.2%) | 0.51 |
Positive | 3 (3.1%) | 9 (11.5%) | 11 (7.4%) | 1 (3.8%) | |||
Lymphovascular invasion | Negative | 86 (88.7%) | 65 (83.3%) | 0.38 | 127 (85.2%) | 24 (92.3%) | 0.54 |
Positive | 11 (11.3%) | 13 (16.7%) | 22 (14.8%) | 2 (7.7%) | |||
Management | |||||||
Thyroidectomy | Unilateral | 40 (41.2%) | 36 (46.2%) | 0.54 | 62 (41.6%) | 14 (53.8%) | 0.29 |
Total/subtotal | 57 (58.8%) | 42 (53.8%) | 87 (58.4%) | 12 (46.2%) | |||
Neck dissection | Negative | 43 (44.3%) | 38 (48.7%) | 0.65 | 67 (45%) | 14 (53.8%) | 0.52 |
Positive | 54 (55.7%) | 40 (51.3%) | 82 (55%) | 12 (46.2%) | |||
Radioiodine ablation | Negative | 68 (70.1%) | 53 (67.9%) | 0.87 | 102 (68.5%) | 19 (73.1%) | 0.82 |
Positive | 29 (29.9%) | 25 (32.1%) | 47 (31.5%) | 7 (26.9%) | |||
External beam radiation therapy | Negative | 84 (86.6%) | 0 (0%) | <0.001 | 72 (48.3%) | 12 (46.2%) | 0.83 |
Positive | 13 (13.4%) | 78 (100%) | 77 (51.7%) | 14 (53.8%) | |||
Follow-up | |||||||
Progression/relapse | Negative | 56 (57.7%) | 45 (57.7%) | 0.99 | 84 (56.4%) | 17 (65.4%) | 0.52 |
Positive | 41 (42.3%) | 33 (42.3%) | 65 (43.6%) | 9 (34.6%) | |||
Recurrence | Negative | 83 (85.6%) | 61 (78.2%) | 0.24 | 120 (80.5%) | 24 (92.3%) | 0.17 |
Positive | 14 (14.4%) | 17 (21.8%) | 29 (19.5%) | 2 (7.7%) | |||
Mortality | Survived | 93 (95.9%) | 74 (94.9%) | 0.75 | 142 (95.3%) | 25 (96.2%) | 0.84 |
Died | 4 (4.1%) | 4 (5.1%) | 7 (4.7%) | 1 (3.8%) |
Patient Characteristics | Levels | Downregulated | Upregulated | p-Value |
---|---|---|---|---|
Total number | 153 | 22 | ||
Demographic data | ||||
Age, years | <55 years | 105 (68.6%) | 14 (63.6%) | 0.63 |
≥55 years | 48 (31.4%) | 8 (36.4%) | ||
Sex | Female | 105 (68.6%) | 14 (63.6%) | 0.63 |
Male | 48 (31.4%) | 8 (36.4%) | ||
Obesity | Negative | 12 (7.8%) | 2 (9.1%) | 0.69 |
Positive | 141 (92.2%) | 20 (90.9%) | ||
Smoking | Negative | 139 (90.8%) | 21 (95.5%) | 0.70 |
Positive | 14 (9.2%) | 1 (4.5%) | ||
Hepatitis C virus | Negative | 78 (51%) | 21 (95.5%) | <0.001 |
Positive | 75 (49%) | 1 (4.5%) | ||
Hashimoto’s thyroiditis | Negative | 131 (85.6%) | 18 (81.8%) | 0.75 |
Positive | 22 (14.4%) | 4 (18.2%) | ||
Genomic mutation | ||||
BRAFV600E mutation | Negative | 90 (58.8%) | 7 (31.8%) | 0.022 |
Positive | 63 (41.2%) | 15 (68.2%) | ||
RAS gene mutation | Negative | 140 (91.5%) | 20 (90.9%) | 0.92 |
Positive | 13 (8.5%) | 2 (9.1%) | ||
Pathological data | ||||
Laterality | Unilateral | 108 (70.6%) | 12 (54.5%) | 0.15 |
Bilateral | 45 (29.4%) | 10 (45.5%) | ||
Focality | Unifocal | 129 (84.3%) | 16 (72.7%) | 0.22 |
Multifocal | 24 (15.7%) | 6 (27.3%) | ||
T stage | T1a | 41 (26.8%) | 6 (27.3%) | 0.93 |
T1b | 41 (26.8%) | 5 (22.7%) | ||
T2 | 60 (39.2%) | 10 (45.5%) | ||
T3 | 7 (4.6%) | 1 (4.5%) | ||
T4 | 4 (2.6%) | 0 (0%) | ||
N stage | N0 | 88 (57.5%) | 13 (59.1%) | 0.89 |
N1 | 65 (42.5%) | 9 (40.9%) | ||
M stage | M0 | 130 (85%) | 15 (68.2%) | 0.06 |
M1 | 23 (15%) | 7 (31.8%) | ||
Pathology stage | Stage Ia | 103 (67.3%) | 12 (54.5%) | 0.51 |
Stage II | 12 (7.8%) | 2 (9.1%) | ||
Stage III | 11 (7.2%) | 1 (4.5%) | ||
Stage IVA | 9 (5.9%) | 2 (9.1%) | ||
Stage IVB | 3 (2%) | 0 (0%) | ||
Stage IVC | 15 (9.8%) | 5 (22.7%) | ||
Extrathyroidal extension | Negative | 121 (79.1%) | 16 (72.7%) | 0.58 |
Positive | 32 (20.9%) | 6 (27.3%) | ||
Perineural invasion | Negative | 149 (97.4%) | 22 (100%) | 0.44 |
Positive | 4 (2.6%) | 0 (0%) | ||
Extranodal extension | Negative | 142 (92.8%) | 21 (95.5%) | 0.65 |
Positive | 11 (7.2%) | 1 (4.5%) | ||
Lymphovascular invasion | Negative | 134 (87.6%) | 17 (77.3%) | 0.19 |
Positive | 19 (12.4%) | 5 (22.7%) | ||
Management | ||||
Thyroidectomy | Unilateral | 65 (42.5%) | 11 (50%) | 0.65 |
Total/subtotal | 88 (57.5%) | 11 (50%) | ||
Neck dissection | Negative | 70 (45.8%) | 11 (50%) | 0.82 |
Positive | 83 (54.2%) | 11 (50%) | ||
Radioiodine ablation | Negative | 104 (68%) | 17 (77.3%) | 0.47 |
Positive | 49 (32%) | 5 (22.7%) | ||
External beam radiation therapy | Negative | 78 (51%) | 6 (27.3%) | 0.042 |
Positive | 75 (49%) | 16 (72.7%) | ||
Follow-up | ||||
Progression/relapse | Negative | 88 (57.5%) | 13 (59.1%) | 0.89 |
Positive | 65 (42.5%) | 9 (40.9%) | ||
Recurrence | Negative | 124 (81%) | 20 (90.9%) | 0.37 |
Positive | 29 (19%) | 2 (9.1%) | ||
Mortality | Survived | 147 (96.1%) | 20 (90.9%) | 0.26 |
Died | 6 (3.9%) | 2 (9.1%) |
Characteristics | Levels | Count | MMP9 | miR–145 | MMP9/miR–145 |
---|---|---|---|---|---|
Demographic data | |||||
Age, years | <55 years | 119 | 2.89 (1.8–8.2) | 0.23 (0.1–0.4) | 16.59 (6–51.3) |
≥55 years | 56 | 4.58 (2–10.7) | 0.22 (0.1–0.5) | 18.16 (9.5–52.4) | |
Sex | Female | 119 | 2.99 (1.7–8.3) | 0.20 (0.1–0.5) | 16.86 (7.5–49.6) |
Male | 56 | 4.46 (2.1–10.3) | 0.26 (0.1–0.5) | 25.05 (6.2–58.5) | |
Obesity | Negative | 14 | 2.86 (1.7–9.8) | 0.33 (0.1–0.8) | 10.90 (3.5–30.7) |
Positive | 161 | 3.36 (1.8–8.7) | 0.22 (0.1–0.4) | 18.65 (7.3–51.7) | |
Smoking | Negative | 160 | 3.31 (1.8–8.7) | 0.22 (0.1–0.4) | 16.73 (6.7–52) |
Positive | 15 | 3.93 (2.1–7.5) | 0.24 (0.2–0.6) | 27.04 (5.4–34.2) | |
Hepatitis C virus | Negative | 99 | 2.33 (1.4–5.2) *** | 0.33 (0.2–0.9) *** | 8.01 (4.4–16.3) *** |
Positive | 76 | 7.53 (2.8–12.2) | 0.11 (0–0.2) | 57.87 (37.8–113) | |
Hashimoto’s thyroiditis | Negative | 149 | 3.36 (1.8–8.6) | 0.23 (0.1–0.4) | 18.65 (7.3–52.6) |
Positive | 26 | 2.70 (1.9–9.7) | 0.24 (0.1–0.5) | 15.15 (4.6–46.2) | |
Genomic mutation | |||||
BRAFV600E mutation | Negative | 97 | 2.99 (1.8–8.9) | 0.20 (0.1–0.3) | 26.45 (7.7–57.9) |
Positive | 78 | 3.88 (1.8–8.4) | 0.26 (0.1–0.8) | 13.29 (4.5–47) | |
RAS gene mutation | Negative | 160 | 3.47 (1.8–8.4) | 0.23 (0.1–0.5) | 17.24 (6.7–51.1) |
Positive | 15 | 2.89 (1.9–9.4) | 0.20 (0.1–0.4) | 28.72 (5.6–75) | |
Pathological data | |||||
Laterality | Unilateral | 120 | 3.23 (1.8–8.6) | 0.23 (0.1–0.4) | 23.70 (5.9–55.3) |
Bilateral | 55 | 3.68 (1.9–8.7) | 0.21 (0.1–0.6) | 14.31 (7–41.7) | |
Focality | Unifocal | 145 | 2.82 (1.7–8.2) * | 0.23 (0.1–0.4) | 16.59 (5.9–51.7) |
Multifocal | 30 | 5.61 (3.2–11.7) | 0.21 (0.1–0.6) | 18.80 (10.4–51) | |
T stage | T1a | 47 | 2.36 (1.4–4.5) ** | 0.26 (0.1–0.5) | 10.03 (4.4–28.7) |
T1b | 46 | 5.86 (2.8–11.5) | 0.26 (0.1–0.7) | 17.24 (8.4–66.4) | |
T2 | 70 | 3.78 (1.7–9.3) | 0.20 (0.1–0.3) | 27.36 (7.5–56.4) | |
T3 | 8 | 2.28 (1.2–7.3) | 0.10 (0–0.3) | 26.44 (13.1–48.9) | |
T4 | 4 | 5.02 (2.5–16.7) | 0.17 (0.1–0.3) | 41.91 (18.1–103.5) | |
N stage | N0 | 101 | 2.25 (1.4–4.3) *** | 0.25 (0.1–0.5) ** | 10.85 (4.6–24.6) *** |
N1 | 74 | 7.84 (3.5–11.8) | 0.19 (0.1–0.3) | 47.65 (16.8–102.4) | |
M stage | M0 | 145 | 2.72 (1.6–7.9) *** | 0.21 (0.1–0.4) | 16.59 (5.9–50.5) |
M1 | 30 | 7.88 (3.8–11.7) | 0.28 (0.1–1) | 27.62 (9.7–56.7) | |
Pathology Stage | Stage Ia | 11 | 2.61 (1.7–7.8) ** | 0.23 (0.1–0.4) | 15.23 (5.6–47.2) |
Stage II | 3 | 7.04 (3.6–12.6) | 0.21 (0.1–0.5) | 43.30 (14.1–125.3) | |
Stage III | 20 | 2.54 (1.6–4.6) | 0.16 (0–0.4) | 22.30 (4.9–51.7) | |
Stage IVA | 115 | 2.19 (1.2–7.9) | 0.10 (0–0.2) | 18.65 (10.1–80.6) | |
Stage IVB | 14 | 17.97 (1.9–0) | 0.34 (0.1–0) | 53.06 (15.1–0) | |
Stage IVC | 12 | 8.05 (4.2–12.1) | 0.34 (0.2–1.1) | 17.27 (9.7–47.2) | |
Extrathyroidal extension | Negative | 137 | 3.07 (1.8–8.3) | 0.22 (0.1–0.4) | 17.67 (6.7–51.7) |
Positive | 38 | 4.13 (1.8–10.6) | 0.24 (0.1–0.9) | 16.46 (7.4–50) | |
Perineural invasion | Negative | 171 | 3.36 (1.8–8.7) | 0.23 (0.1–0.5) | 16.86 (6.6–50.4) |
Positive | 4 | 2.85 (2.4–9.9) | 0.15 (0–0.3) | 49.84 (16.4–73.2) | |
Extranodal extension | Negative | 163 | 3.22 (1.8–8.4) | 0.23 (0.1–0.5) | 16.59 (6.6–49.6) |
Positive | 12 | 6.24 (2.1–12.2) | 0.15 (0–0.3) | 42.62 (19.3–64.7) | |
Lymphovascular invasion | Negative | 151 | 2.89 (1.8–8.2) | 0.23 (0.1–0.5) | 16.59 (6–49.6) |
Positive | 24 | 6.85 (3.3–11.1) | 0.17 (0.1–0.8) | 33.00 (10.5–64.7) | |
Follow-up | |||||
Progression/relapse | Negative | 101 | 2.12 (1.4–3.9) *** | 0.25 (0.1–0.5) * | 10.28 (4.6–24.2) *** |
Positive | 74 | 8.05 (3.9–12.4) | 0.21 (0.1–0.3) | 48.57 (17.5–106.6) | |
Recurrence | Negative | 144 | 2.83 (1.6–7.8) ** | 0.25 (0.1–0.5) ** | 13.64 (5.7–37.3) *** |
Positive | 31 | 7.90 (3.2–13.1) | 0.09 (0–0.2) | 83.78 (34.2–122.4) | |
Mortality | Survived | 167 | 3.27 (1.8–8.4) | 0.23 (0.1–0.5) | 17.62 (6.7–52.2) |
Died | 8 | 3.91 (1.6–10.3) | 0.24 (0.1–0.9) | 22.66 (5.5–44.5) |
Comparison | Cohort | Control | Cases | AUC | Sensitivity | Specificity | p-Value |
---|---|---|---|---|---|---|---|
Nodal metastasis vs. none | Overall | 101 | 74 | 0.791 | 73.0 | 72.3 | <0.001 |
BRAF− | 54 | 43 | 0.854 | 86.0 | 70.4 | <0.001 | |
BRAF+ | 47 | 31 | 0.722 | 54.8 | 74.5 | <0.001 | |
HT− | 83 | 66 | 0.798 | 72.7 | 72.3 | <0.001 | |
HT+ | 18 | 8 | 0.757 | 75.0 | 72.2 | 0.040 | |
Progression/relapse vs. none | Overall | 101 | 74 | 0.812 | 74.3 | 73.3 | <0.001 |
BRAF− | 56 | 41 | 0.892 | 90.2 | 71.4 | <0.001 | |
BRAF+ | 45 | 33 | 0.733 | 54.5 | 75.6 | <0.001 | |
HT− | 84 | 65 | 0.797 | 72.3 | 71.4 | <0.001 | |
HT+ | 17 | 9 | 0.895 | 88.9 | 82.4 | 0.001 | |
Recurrence vs. none | Overall | 61 | 17 | 0.807 | 70.6 | 72.1 | <0.001 |
BRAF− | 83 | 14 | 0.827 | 92.9 | 51.8 | <0.001 | |
BRAF+ | 61 | 17 | 0.817 | 70.6 | 72.1 | <0.001 | |
HT− | 120 | 29 | 0.814 | 82.8 | 60.8 | <0.001 | |
HT+ | 24 | 2 | 0.750 | 50.0 | 58.3 | 0.25 |
Characteristics | n (%) | Tissue | Pre-Plasma | Post-Plasma | p-Value (Pre vs. Tissue) | p-Value (Post vs. Pre) | |
---|---|---|---|---|---|---|---|
PTC patients | Overall | 86 (100) | 17.6 (5.3–64.0) | 2.39 (0.61–9.71) | 0.74 (0.24–2.25) | <0.001 | 0.011 |
LNM | Negative | 44 (52.2) | 7.8 (3.9–18.1) | 1.34 (0.36–4.2) | 0.91 (0.22–2.60) | <0.001 | 0.41 |
Positive | 42 (48.8) | 56.9 (21.4–116) | 6.65 (1.98–11.6) | 0.57 (0.24–1.76) | <0.001 | 0.026 | |
Extrathyroidal extension | Negative | 67 (77.9) | 23.1 (6.0–63.58) | 0.74 (0.22–1.78) | 2.15 (0.42–4.96) | <0.001 | 0.013 |
Positive | 19 (22.1) | 2.61 (0.75–10.6) | 16.3 (4.53–65.5) | 0.70 (0.43–4.40) | <0.001 | 1.0 | |
Progression/relapse | Negative | 47 (54.7) | 7.7 (3.97–18.65) | 0.90 (0.22–2.68) | 7.81 (2.61–13.4) | 0.028 | 0.37 |
Positive | 39 (45.3) | 1.32 (0.37–3.40) | 59.2 (27.0–119) | 0.6 (0.25–1.77) | <0.001 | <0.001 | |
Recurrence | Negative | 69 (80.2) | 13.27 (4.6–43.0) | 1.81 (0.52–7.62) | 0.83 (0.26–2.27) | <0.001 | 0.07 |
Positive | 17 (19.8) | 162.2 (93.9–182) | 13.9 (8.27–17.8) | 2.26 (0.52–5.79) | <0.001 | 0.18 | |
Died | Negative | 82 (95.3) | 17.4 (5.27–64.1) | 0.73 (0.24–2.25) | 3.98 (1.01–9.99) | <0.001 | 0.009 |
Positive | 4 (4.7) | 2.17 (0.62–9.72) | 6.5 (5.8–14.1) | 1.03 (0.35–11.2) | 0.10 | 1.0 |
Ref. | Author | Year | Country | Source | Type | PTC | LNM | TNM | Size | M1 | ETE | SPRD |
---|---|---|---|---|---|---|---|---|---|---|---|---|
[61] | Roncevic | 2022 | Serbia | Tissue | Protein/RNA | 50 | • | • | ||||
[78] | EH Kusumastuti | 2021 | Indonesia | Tissue | Protein | 43 | • | |||||
[62] | Liu Xincheng | 2020 | China | Tissue | Protein | 104 | • | • | ||||
[73] | Dobrescu R | 2020 | Romania | Serum | Protein | 97 | • | |||||
[63] | Li Na | 2019 | China | Tissue | Protein | 40 | • | |||||
[64] | Roncevic J | 2019 | Serbia | Tissue | Protein/RNA | 105 | • | • | • | • | ||
[77] | XingKai Liu | 2019 | China | Tissue | Protein | 112 | • | • | • | • | ||
[65] | Dahai Xu | 2019 | China | Serum | Protein | 182 | • | • | • | • | • | • |
[83] | Boris Bumber | 2020 | Croatia | Tissue | Protein | 159 | • | |||||
[74] | Zhang | 2019 | China | Serum | Protein | 57 | • | • | • | |||
[84] | Maryam Zarkesh | 2018 | Iran | Tissue | Protein/RNA | 60 | • | |||||
[62] | Chen Suqin | 2018 | China | Tissue | Protein | 200 | • | • | • | |||
[66] | Wei Tian | 2017 | China | Tissue | Protein | 88 | • | • | ||||
[21] | Ilona Marecko | 2014 | Serbia | Tissue | Protein | 120 | • | • | ||||
[67] | Ni Wang | 2014 | China | Tissue | Protein | 83 | • | • | • | |||
[68] | Yang Lei | 2014 | China | Tissue | Protein | 72 | • | • | ||||
[69] | Meng Xian-Ying | 2014 | China | Tissue | Protein | 66 | • | • | • | |||
[62] | Liu Zhen | 2014 | China | Tissue | Protein | 164 | • | • | • | |||
[67] | Ni Wang | 2013 | China | Tissue | Protein/RNA | 83 | • | • | ||||
[70] | Huang Pei | 2013 | China | Tissue | Protein | 58 | • | |||||
[67] | Xianying Meng | 2012 | China | Tissue | Protein/RNA | 66 | • | • | ||||
[62] | Dong Yuhong | 2012 | China | Tissue | Protein | 168 | • | • | ||||
[62] | Wang Zhaohui | 2012 | China | Tissue | Protein | 56 | • | • | ||||
[71] | Shi Jianhua | 2010 | China | Tissue | Protein | 157 | • | |||||
[62] | Zhang Jie | 2010 | China | Tissue | Protein | 74 | • | |||||
[79] | Buergy | 2009 | Germany | Tissue | Protein | 67 | • | |||||
[75] | Shih Lin | 2003 | Taiwan | Plasma | Protein | 30 | • | • | • | • | • |
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Toraih, E.A.; Hussein, M.H.; Al Ageeli, E.; Ellaban, M.; Kattan, S.W.; Moroz, K.; Fawzy, M.S.; Kandil, E. Matrix Metalloproteinase 9/microRNA-145 Ratio: Bridging Genomic and Immunological Variabilities in Thyroid Cancer. Biomedicines 2023, 11, 2953. https://doi.org/10.3390/biomedicines11112953
Toraih EA, Hussein MH, Al Ageeli E, Ellaban M, Kattan SW, Moroz K, Fawzy MS, Kandil E. Matrix Metalloproteinase 9/microRNA-145 Ratio: Bridging Genomic and Immunological Variabilities in Thyroid Cancer. Biomedicines. 2023; 11(11):2953. https://doi.org/10.3390/biomedicines11112953
Chicago/Turabian StyleToraih, Eman A., Mohamed H. Hussein, Essam Al Ageeli, Mohamad Ellaban, Shahd W. Kattan, Krzysztof Moroz, Manal S. Fawzy, and Emad Kandil. 2023. "Matrix Metalloproteinase 9/microRNA-145 Ratio: Bridging Genomic and Immunological Variabilities in Thyroid Cancer" Biomedicines 11, no. 11: 2953. https://doi.org/10.3390/biomedicines11112953