Prognostic and Clinicopathological Significance of the Aberrant Expression of β-Catenin in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Protocol
2.2. Search Strategy
2.3. Eligibility Criteria
2.4. Study Selection Process
2.5. Data Extraction
2.6. Evaluation of Quality and Risk of Bias
2.7. Statistical Analysis
2.8. Validation of Methodological Quality
3. Results
3.1. Results of the Literature Search
3.2. Study Characteristics
3.3. Qualitative Evaluation
3.3.1. Study Participation
3.3.2. Study Attrition
3.3.3. Prognostic Factor Measurement
3.3.4. Outcome Measurement
3.3.5. Study Confounding
3.3.6. Statistical Analysis and Reporting
3.4. Quantitative Evaluation (Meta-Analysis)
3.4.1. Association between the Aberrant Expression of β-Catenin and Prognostic Variables
Overall Survival (OS)
Disease-Free Survival (DFS)
3.4.2. Association between the Aberrant Expression of β-Catenin and Clinicopathological Variables
T Status
N Status
Clinical Stage
Histological Grade
3.5. Quantitative Evaluation (Variables Not Included in Meta-Analysis)
3.6. Quantitative Evaluation (Secondary Analyses)
3.6.1. Analysis of Subgroups
3.6.2. Meta-Regression Analysis
3.6.3. Sensitivity Analysis
3.6.4. Analysis of Small-Study Effects
3.7. Validation of Methodological Quality
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Total | 41 Studies |
---|---|
Year of publication | 1998–2021 |
Total patients (range) | 2746 (12–290) |
β-catenin aberrant subcellular location | |
Cell membrane loss | 11 studies |
Cytoplasmic-nuclear expression | 21 studies |
Not defined in primary-level studies | 9 studies |
Study design | |
Retrospective cohort | 41 studies |
Experimental methods for β-catenin expression determination | |
Immunohistochemistry | 41 studies |
Anti-β-catenin antibody | |
Clone 14 | 6 studies |
sc-7963 | 2 studies |
C19220 | 2 studies |
Other | 10 studies |
Not reported | 21 studies |
Anti-β-catenin antibody dilution | |
<1:250 | 22 studies |
1:500–1000 | 7 studies |
Not reported | 12 studies |
Anti- β-catenin antibody incubation time | |
Overnight | 15 studies |
1 h | 13 studies |
Not reported | 13 studies |
Anti-β-catenin antibody incubation temperature | |
4 °C | 13 studies |
Room temperature or higher | 13 studies |
Not reported | 15 studies |
Geographical region | |
Asian countries | 29 studies |
Non-Asian countries | 12 studies |
Meta-Analyses | No. of Studies | No. of Patients | Stat. Model | Wt | Pooled Data | Heterogeneity | Supplementary Materials a | ||
---|---|---|---|---|---|---|---|---|---|
ES (95% CI) | p-Value | Phet | I2 (%) | ||||||
Survival Parameters | |||||||||
Overall Survival | |||||||||
Aberrant β-catenin expression (all) b | 10 | 938 | REM | DL | HR = 1.77 (1.20–2.60) | 0.004 | 0.004 | 62.4 | Manuscript, Figure 3 |
Subgroup analysis by differential subcellular location c | Figure 3 | ||||||||
Loss of cell membrane | 4 | 460 | REM | DL | HR = 2.37 (1.55–3.62) | <0.001 | 0.27 | 23.9 | |
Nuclear-cytoplasmic expression | 3 | 255 | REM | DL | HR = 1.98 (0.93–4.22) | 0.07 | 0.10 | 56.1 | |
Not defined in primary-level studies | 3 | 223 | REM | DL | HR = 0.89 (0.62–1.28) | 0.53 | 0.40 | 0.0 | |
Subgroup analysis by geographical area c | Figure S1 | ||||||||
Asian | 8 | 772 | REM | DL | HR = 1.81 (1.10–3.00) | 0.02 | 0.001 | 70.1 | |
Non-Asian | 2 | 166 | REM | DL | HR = 1.72 (1.09–2.71) | 0.02 | 0.80 | 0.0 | |
Subgroup analysis by anti-β-catenin antibody c | Figure S2 | ||||||||
Clone-14 | 2 | 294 | REM | DL | HR = 3.57 (2.03–6.29) | <0.001 | 1.00 | 0.0 | |
Sc-7963 | 2 | 143 | REM | DL | HR = 0.79 (0.52–1.20) | 0.27 | 0.46 | 0.0 | |
Other | 2 | 190 | REM | DL | HR = 1.82 (0.87–3.81) | 0.11 | 0.18 | 44.7 | |
Not reported | 4 | 311 | REM | DL | HR = 1.56 (1.10–2.22) | 0.01 | 0.37 | 3.9 | |
Subgroup analysis by anti-β-catenin antibody dilution c | Figure S3 | ||||||||
<1:250 | 5 | 545 | REM | DL | HR = 2.81 (1.87–4.22) | <0.001 | 0.72 | 0.0 | |
1:500–1000 | 3 | 230 | REM | DL | HR = 1.65 (1.10–2.47) | 0.02 | 0.37 | 0.0 | |
Not reported | 2 | 163 | REM | DL | HR = 0.90 (0.60–1.34) | 0.60 | 0.25 | 26.0 | |
Subgroup analysis by anti-β-catenin antibody incubation time c | Figure S4 | ||||||||
1 h | 3 | 273 | REM | DL | HR = 1.23 (0.64–2.36) | 0.53 | 0.03 | 72.9 | |
Overnight | 6 | 585 | REM | DL | HR = 2.31 (1.65–3.23) | <0.001 | 0.43 | 0.0 | |
Not reported | 1 | 80 | - | - | HR = 1.28 (0.62–2.65) | 0.51 | - | - | |
Subgroup analysis by anti-β-catenin antibody incubation temperature c | Figure S5 | ||||||||
4 °C | 6 | 585 | REM | DL | HR = 2.31 (1.65–3.23) | <0.001 | 0.43 | 0.0 | |
Room temperature or higher | 3 | 273 | REM | DL | HR = 1.23 (0.64–2.36) | 0.53 | 0.03 | 72.9 | |
Not reported | 1 | 80 | - | - | HR = 1.28 (0.62–2.65) | 0.51 | - | - | |
Subgroup analysis by overall risk of bias in primary-level studies c | Figure S6 | ||||||||
Low RoB | 3 | 404 | REM | DL | HR = 3.28 (2.05–5.24) | <0.001 | 0.87 | 0.0 | |
Moderate-High RoB | 7 | 534 | REM | DL | HR = 1.29 (0.91–1.83) | 0.15 | 0.14 | 38.5 | |
Univariable meta-regressions by study design and patients’ characteristics d | |||||||||
Follow up (months, mean) | 7 | 618 | random-effects meta-regression | Coef = 0.016 (−0.033 to 0.065) | 0.47 ± 0.005 e | hetexplained = −1.02% f | Figure S7 | ||
Sex (proportion of males, %) | 10 | 938 | random-effects meta-regression | Coef = −0.005 (−0.035 to 0.024) | 0.69 ± 0.005 e | hetexplained = −17.95% f | Figure S8 | ||
Age (years, mean) | 9 | 858 | random-effects meta-regression | Coef = 0.132 (0.034 to 0.229) | 0.02 ± 0.002 e | hetexplained = 79.62% f | Figure S9 | ||
Clinical stage (proportion of stage-III/IV patients, %) | 5 | 469 | random-effects meta-regression | Coef = 0.001 (−0.078 to 0.079) | 0.99 ± 0.001 e | hetexplained = −38.30% f | Figure S10 | ||
Tobacco consumption (proportion of smokers, %) | 2 | 141 | random-effects meta-regression | - | - | - | - | ||
Areca nut/Betel quid consumption (proportion of chewers, %) | 0 | 0 | - | - | - | - | - | ||
Alcohol consumption (% of patients with positive habits) | 2 | 141 | - | - | - | - | - | ||
Disease-free survival | |||||||||
Aberrant β-catenin expression (all) b | 5 | 379 | REM | DL | HR = 2.44 (1.10–5.40) | 0.03 | <0.001 | 88.6 | Figure S11 |
Clinicopathological Characteristics | |||||||||
T Status | |||||||||
Aberrant β-catenin expression (all) b | 10 | 1418 | REM | DL | OR = 1.76 (1.23–2.53) | 0.004 | 0.06 | 37.1 | Figure S12 |
Subgroup analysis by differential subcellular location c | Figure S12 | ||||||||
Loss of cell membrane | 7 | 673 | REM | DL | OR = 1.81 (1.05–3.11) | 0.03 | 0.08 | 47.7 | |
Nuclear-cytoplasmic expression | 7 | 542 | REM | DL | OR = 1.93 (0.91–4.06) | 0.09 | 0.05 | 53.0 | |
Not defined in primary-level studies | 4 | 203 | REM | DL | OR = 1.42 (0.68–2.97) | 0.35 | 0.50 | 0.0 | |
N Status | |||||||||
Aberrant β-catenin expression (all) b | 23 | 1881 | REM | DL | OR = 2.39 (1.68–3.40) | <0.001 | 0.002 | 53.0 | Figure S13 |
Subgroup analysis by differential subcellular location c | Figure S13 | ||||||||
Loss of cell membrane | 9 | 769 | REM | DL | OR = 3.44 (2.40–4.93) | <0.001 | 0.44 | 0.0 | |
Nuclear-cytoplasmic expression | 9 | 849 | REM | DL | OR = 1.67 (0.93–3.00) | 0.08 | 0.01 | 59.1 | |
Not defined in primary-level studies | 5 | 263 | REM | DL | OR = 1.97 (0.88–4.38) | 0.10 | 0.18 | 36.7 | |
Clinical Stage | |||||||||
Aberrant β-catenin expression (all) b | 15 | 1165 | REM | DL | OR = 2.40 (1.58–3.63) | <0.001 | 0.03 | 45.6 | Figure S14 |
Subgroup analysis by differential subcellular location c | Figure S14 | ||||||||
Loss of cell membrane | 6 | 514 | REM | DL | OR = 2.51 (1.17–5.35) | 0.02 | 0.01 | 66.7 | |
Nuclear-cytoplasmic expression | 5 | 426 | REM | DL | OR = 3.12 (1.81–5.40) | <0.001 | 0.50 | 0.0 | |
Not defined in primary-level studies | 4 | 225 | REM | DL | OR = 1.49 (0.66–3.36) | 0.33 | 0.21 | 33.5 | |
Histological Grade | |||||||||
Aberrant β-catenin expression (all) b | 32 | 1974 | REM | DL | OR = 1.57 (1.09–2.25) | 0.02 | <0.001 | 55.1 | Figure S15 |
Subgroup analysis by differential subcellular location c | Figure S15 | ||||||||
Loss of cell membrane | 7 | 604 | REM | DL | OR = 1.77 (0.82–3.83) | 0.14 | 0.002 | 71.9 | |
Nuclear-cytoplasmic expression | 17 | 986 | REM | DL | OR = 1.76 (1.23–2.53) | 0.002 | 0.33 | 10.2 | |
Not defined in primary-level studies | 8 | 384 | REM | DL | OR = 0.99 (0.36–2.76) | 0.99 | <0.001 | 73.4 |
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Ramos-García, P.; González-Moles, M.Á. Prognostic and Clinicopathological Significance of the Aberrant Expression of β-Catenin in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis. Cancers 2022, 14, 479. https://doi.org/10.3390/cancers14030479
Ramos-García P, González-Moles MÁ. Prognostic and Clinicopathological Significance of the Aberrant Expression of β-Catenin in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis. Cancers. 2022; 14(3):479. https://doi.org/10.3390/cancers14030479
Chicago/Turabian StyleRamos-García, Pablo, and Miguel Á. González-Moles. 2022. "Prognostic and Clinicopathological Significance of the Aberrant Expression of β-Catenin in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis" Cancers 14, no. 3: 479. https://doi.org/10.3390/cancers14030479