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Prognostic and Clinicopathological Significance of FADD Upregulation in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

1
School of Dentistry, University of Granada, 18071 Granada, Spain
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Instituto de Investigación Biosanitaria ibs.Granada, 18012 Granada, Spain
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Dermatology Service, San Cecilio Hospital Complex, 18016 Granada, Spain
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Dermatology Service, Ciudad Real General University Hospital, 13005 Ciudad Real, Spain
5
Pathology Service, San Cecilio Hospital Complex, 18016 Granada, Spain
*
Authors to whom correspondence should be addressed.
Cancers 2020, 12(9), 2393; https://doi.org/10.3390/cancers12092393
Received: 17 June 2020 / Revised: 13 July 2020 / Accepted: 7 August 2020 / Published: 24 August 2020
(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)
Fas-associated death domain (FADD) upregulation, i.e., gene amplification, protein phosphorylation and/or overexpression, has shown promising prognostic implications in head and neck squamous cell carcinoma (HNSCC). This systematic review and meta-analysis aims to evaluate the clinicopathological and prognostic significance of FADD upregulation in HNSCC. We searched studies published before February 2020 through PubMed, Embase, Web of Science, Scopus and Google Scholar. We evaluated the quality of the studies included using the QUIPS tool. The impact of FADD upregulation on survival and clinicopathological variables was meta-analysed. We explored heterogeneity and their sources, conducted sensitivity analyses and investigated small-study effects. Thirteen studies (1,923 patients) met inclusion criteria. FADD immunohistochemical overexpression was statistically associated with worse overall survival (hazard ratio [HR] = 1.52, 95% confidence intervals [CI] = 1.28–1.81, p < 0.001), disease-specific survival (HR = 2.52, 95% CI = 1.61–3.96, p < 0.001), disease-free survival (HR = 1.67, 95% CI=1.29–2.15, p < 0.001), higher clinical stage (odds ratio [OR] = 1.72, 95% CI = 1.17–2.51, p = 0.005) and a large magnitude of effect with N+ status (OR = 2.36, 95% CI = 1.85–3.00, p < 0.001). FADD phosphorylation in ser-194 demonstrated no prognostic value, while no conclusive results can be drawn for FADD gene amplification. In conclusion, our findings indicate that immunohistochemical assessment of FADD overexpression could be incorporated into the prognostic evaluation of HNSCC. View Full-Text
Keywords: FADD; Fas-associated death domain; head and neck squamous cell carcinoma; oral squamous cell carcinoma; laryngeal squamous cell carcinoma; prognosis; biomarker; systematic review; meta-analysis FADD; Fas-associated death domain; head and neck squamous cell carcinoma; oral squamous cell carcinoma; laryngeal squamous cell carcinoma; prognosis; biomarker; systematic review; meta-analysis
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MDPI and ACS Style

González-Moles, M.Á.; Ayén, Á.; González-Ruiz, I.; de Porras-Carrique, T.; González-Ruiz, L.; Ruiz-Ávila, I.; Ramos-García, P. Prognostic and Clinicopathological Significance of FADD Upregulation in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis. Cancers 2020, 12, 2393. https://doi.org/10.3390/cancers12092393

AMA Style

González-Moles MÁ, Ayén Á, González-Ruiz I, de Porras-Carrique T, González-Ruiz L, Ruiz-Ávila I, Ramos-García P. Prognostic and Clinicopathological Significance of FADD Upregulation in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis. Cancers. 2020; 12(9):2393. https://doi.org/10.3390/cancers12092393

Chicago/Turabian Style

González-Moles, Miguel Á., Ángela Ayén, Isábel González-Ruiz, Teresa de Porras-Carrique, Lucía González-Ruiz, Isábel Ruiz-Ávila, and Pablo Ramos-García. 2020. "Prognostic and Clinicopathological Significance of FADD Upregulation in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis" Cancers 12, no. 9: 2393. https://doi.org/10.3390/cancers12092393

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