Significance of the Overexpression of Substance P and Its Receptor NK-1R in Head and Neck Carcinogenesis: 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. Data Extraction
2.5. Evaluation of Quality and Risk of Bias
2.6. Statistical Analysis
3. Results
3.1. Literature Search
3.2. Study Characteristics
3.3. Qualitative Evaluation
3.4. Quantitative Evaluation (Meta-Analysis)
3.4.1. Differential Expression of SP/NK-1R in Head & Neck Tumorigenesis
3.4.2. Differential Expression of SP/NK-1R in Benign Tumors
3.4.3. Differential Expression of SP/NK-1R in Pre-Malignant Tissues
3.4.4. Differential Expression of SP/NK-1R in Pre-Malignant Tissues
3.5. Quantitative Evaluation (Secondary Analyses)
3.5.1. Sensitivity Analysis
3.5.2. Analysis of Small-Study Effects
3.6. Biological and Oncogenic Roles of SP/NK-1R
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Total | 16 Studies |
---|---|
Year of publication | 1983–2020 |
Number of cases | |
Total | 909 |
Sample size, range | 5–114 |
Biomarkers analyzed * | |
SP | 15 studies (897 cases) |
NK-1R | 7 studies (411 cases) |
Affected sites | |
Oral cavity | 4 studies (285 cases) |
Nasal cavity | 1 study (20 cases) |
Larynx | 2 studies (233 cases) |
Salivary glands | 1 study (171 cases) |
Thyroid gland | 6 studies (142 cases) |
Head and neck mixed | 2 studies (58 cases) |
Type of tumors * | |
Benign | 5 studies (226 cases) |
Pre-malignant | 3 studies (230 cases) |
Malignant | 11 studies (453 cases) |
Study design | |
Retrospective cohort | 16 studies |
Geographical region | |
Europe | 11 studies (610 patients) |
Asia | 3 studies (216 cases) |
North-Central America | 2 studies (83 cases) |
Pooled Data | Heterogeneity | ||||||||
---|---|---|---|---|---|---|---|---|---|
Meta-Analyses | No. of Studies * | No. of Tumors | Stat. Model | Wt | PP (95% CI) | p-Value | Phet | I2 (%) | Supplementary Materialsa |
1. All tumors | |||||||||
All b | 38 | 1308 | REM | D-L | 40.52% (24.23–57.78) | ── | <0.001 | 96.89 | Figure 3 |
Classification of tumors by malignant behavior c | 0.004 d | Figure 3 | |||||||
Benign | 9 | 289 | REM | D-L | 11.86% (1.23–28.31) | <0.001 | 88.2 | ||
Pre-malignant | 6 | 460 | REM | D-L | 69.25% (35.34–94.52) | <0.001 | 98.2 | ||
Malignant | 23 | 559 | REM | D-L | 45.04% (22.54, 68.48) | <0.001 | 95.8 | ||
Classification of tumors by malignant behavior —combining the pre-malignant and malignant groups- c | 0.002 d | Figure S1, p. 6 | |||||||
Benign | 9 | 289 | REM | D-L | 11.86% (1.23–28.31) | <0.001 | 88.2 | ||
Non-Benign | 29 | 1019 | REM | D-L | 50.93% (32.13–69.61) | <0.001 | 96.6 | ||
Paired analysis by malignant behavior | 0.003 | Figure S2, p. 7 | |||||||
Benign | 9 | 289 | REM | D-L | 11.86% (1.23–28.31) | <0.001 | 88.2 | ||
Pre-malignant | 6 | 460 | REM | D-L | 69.25% (35.34–94.52) | <0.001 | 98.2 | ||
Paired analysis by malignant behavior | 0.02 | Figure S3, p. 8 | |||||||
Benign | 9 | 289 | REM | D-L | 11.86% (1.23–28.31) | <0.001 | 88.2 | ||
Malignant | 23 | 559 | REM | D-L | 45.04% (22.54, 68.48) | <0.001 | 95.8 | ||
Paired analysis by malignant behavior | 0.24 | Figure S4, p. 9 | |||||||
Pre-malignant | 6 | 460 | REM | D-L | 69.25% (35.34–94.52) | <0.001 | 98.2 | ||
Malignant | 23 | 559 | REM | D-L | 45.04% (22.54, 68.48) | <0.001 | 95.8 | ||
2. Benign tumors | |||||||||
Benign tumors by geographical area c | <0.001 d | Figure S5, p. 10 | |||||||
Asian | 4 | 112 | REM | D-L | 0.00% (0.00–0.00) | 0.74 | 0.0 | ||
Non-Asian | 5 | 177 | REM | D-L | 26.43% (15.41–39.01) | 0.04 | 60.96 | ||
Benign tumors by anatomical site c | <0.001 d | Figure S6, p. 11 | |||||||
Larynx | 1 | 11 | ── | ── | 36.36% (15.17–64.62) | ── | ── | ||
Nasal cavity | 1 | 20 | ── | ── | 25.00% (11.19–46.87) | ── | ── | ||
Oral cavity | 2 | 128 | REM | D-L | 21.88% (15.04–29.56) | ── | ── | ||
Salivary gland | 4 | 112 | REM | D-L | 0.00% (0.00–0.00) | 0.76 | 0.0 | ||
Head and neck mixed | 1 | 18 | ── | ── | 38.89% (20.31–61.38) | ── | ── | ||
Benign tumors by histological type c | <0.001 d | Figure S7, p. 12 | |||||||
Glandular | 4 | 112 | REM | D-L | 0.00% (0.00–0.00) | 0.76 | 0.0 | ||
Squamous | 4 | 159 | REM | D-L | 24.17% (12.56–37.86) | 0.04 | 64.01 | ||
Nervous | 1 | 18 | ── | ── | 38.89% (20.31–61.38) | ── | ── | ||
Benign tumors by biomarker c | 0.85 d | Figure S8, p. 13 | |||||||
SP | 8 | 226 | REM | D-L | 11.77% (0.11–32.64) | <0.001 | 89.64 | ||
NK-1R | 1 | 63 | ── | ── | 12.70% (6.58–23.11) | ── | ── | ||
3. Pre-malignant tissues | |||||||||
Pre-malignant tissues by geographical area c | ── | ── | |||||||
Asian | 0 | 0 | ── | ── | ── | ── | ── | ||
Non-Asian | 6 | 460 | REM | D-L | 69.25% (35.34–94.52) | <0.001 | 98.2 | ||
Pre-malignant tissues by anatomical site c | 0.02 d | Figure S9, p. 14 | |||||||
Larynx | 2 | 194 | REM | D-L | 94.42% (90.63–97.34) | ── | ── | ||
Oral cavity | 4 | 266 | REM | D-L | 52.24% (13.57–89.40) | 0.001 | 97.94 | ||
Pre-malignant tissues by histological type c | ── | ── | |||||||
Squamous | 6 | 460 | REM | D-L | 69.25% (35.34–94.52) | <0.001 | 98.2 | ||
Other | 0 | 0 | ── | ── | ── | ── | ── | ||
Pre-malignant tissues by clinical type c | <0.001 d | Figure S10, p. 15 | |||||||
OLP | 2 | 100 | REM | D-L | 61.30% (51.45–70.72) | ── | ── | ||
ANTE-OSCC | 2 | 166 | REM | D-L | 43.27% (35.78–50.93) | ── | ── | ||
ANTE-LSCC | 2 | 194 | REM | D-L | 94.42% (90.63–97.34) | ── | ── | ||
Pre-malignant tissues by biomarker c | 0.13 d | Figure S11, p. 16 | |||||||
SP | 3 | 230 | REM | D-L | 89.60% (66.10–100.00) | <0.001 | 94.77 | ||
NK-1R | 3 | 230 | REM | D-L | 43.92% (1.33–93.97) | <0.001 | 98.75 | ||
4. Malignant tumors | |||||||||
Malignant tumors by geographical area c | 0.007 d | Figure S12, p. 17 | |||||||
Asian | 8 | 104 | REM | D-L | 12.04% (0.00–35.87) | <0.001 | 83.55 | ||
Non-Asian | 15 | 455 | REM | D-L | 65.03% (34.63–90.69) | <0.001 | 96.81 | ||
Malignant tumors by anatomical site c | <0.001 d | Figure S13, p. 18 | |||||||
Larynx | 3 | 125 | REM | D-L | 67.80% (8.94–100.00) | <0.001 | 90.58 | ||
Oral cavity | 2 | 173 | REM | D-L | 64.14% (56.80–71.17) | ── | ── | ||
Salivary gland | 6 | 59 | REM | D-L | 3.84% (0.00–12.24) | 0.55 | 0.0 | ||
Thyroid gland | 11 | 162 | REM | D-L | 63.25% (22.83–96.04) | <0.001 | 95.15 | ||
Head and neck mixed | 1 | 4 | ── | ── | 62.50% (47.03–75.78) | ── | ── | ||
Malignant tumors by histological type c | 0.16 d | Figure S14, p. 19 | |||||||
Glandular | 17 | 221 | REM | D-L | 37.31% (12.70–65.25) | <0.001 | 92.71 | ||
Squamous | 4 | 327 | REM | D-L | 74.83% (47.01–94.77) | <0.001 | 96.27 | ||
Neuroendocrine | 2 | 11 | REM | D-L | 51.42% (19.04–83.29) | ── | ── | ||
Malignant tumors by biomarker c | 0.02 d | Figure S15, p. 20 | |||||||
SP | 18 | 441 | REM | D-L | 33.60% (9.13–62.90) | <0.001 | 96.57 | ||
NK-1R | 5 | 118 | REM | D-L | 83.67% (51.40–100.00) | <0.001 | 84.57 |
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González-Moles, M.Á.; Ramos-García, P.; Esteban, F. Significance of the Overexpression of Substance P and Its Receptor NK-1R in Head and Neck Carcinogenesis: A Systematic Review and Meta-Analysis. Cancers 2021, 13, 1349. https://doi.org/10.3390/cancers13061349
González-Moles MÁ, Ramos-García P, Esteban F. Significance of the Overexpression of Substance P and Its Receptor NK-1R in Head and Neck Carcinogenesis: A Systematic Review and Meta-Analysis. Cancers. 2021; 13(6):1349. https://doi.org/10.3390/cancers13061349
Chicago/Turabian StyleGonzález-Moles, Miguel Ángel, Pablo Ramos-García, and Francisco Esteban. 2021. "Significance of the Overexpression of Substance P and Its Receptor NK-1R in Head and Neck Carcinogenesis: A Systematic Review and Meta-Analysis" Cancers 13, no. 6: 1349. https://doi.org/10.3390/cancers13061349
APA StyleGonzález-Moles, M. Á., Ramos-García, P., & Esteban, F. (2021). Significance of the Overexpression of Substance P and Its Receptor NK-1R in Head and Neck Carcinogenesis: A Systematic Review and Meta-Analysis. Cancers, 13(6), 1349. https://doi.org/10.3390/cancers13061349