title: mTOR pathway protein immunoexpression as a prognostic factor for survival in head and neck cancer patients: a systematic review and meta-analysis.
abstract: BACKGROUND
  Several mTOR pathway proteins are involved in the regulation of cellular anabolism, growth, proliferation, and survival. Activated proteins in the mTOR pathway are deregulated in multiple types of cancers and could influence prognosis. However, it is unclear whether deregulation of mTOR pathway proteins serves a prognostic role in patients with head and neck cancer (HNC). Furthermore, proteins in the mTOR pathway may be important targets for anticancer therapy. The aim of this study was to summarize existing cohort studies to determine whether immunoexpression of mTOR pathway proteins are important prognostic factors for survival in patients with HNC.
  
  
  METHODS
  A systematic review was performed using the Cochrane, Lilacs, PubMed, ScienceDirect, Scopus, and Web of Science databases (up to 23 January 2015). A meta-analysis was conducted to measure the frequency of protein expression in head and neck cancer patient samples and the prognostic value of mTOR pathway proteins for overall survival (OS) and disease-free survival (DFS).
  
  
  RESULTS
  Twelve studies were included in our final analysis. The meta-analysis revealed that the frequency of overall expression of mTOR pathway proteins was 74.42% (CI: 63.3 to 84.0, P < 0.001, n = 2016 samples). The survival meta-analysis showed a pooled hazard ratio for OS and DFS of 1.44 (95% confidence interval [95% CI] 1.14-1.73) and 1.18 (95% CI 0.71-1.64), respectively.
  
  
  CONCLUSIONS
  This systematic review and meta-analysis support evidence that mTOR pathway proteins can be used as predictive markers for survival in patients with HNC because their expression was significantly associated with poor OS and short DFS.
authors.affiliation: Oral Histopathology Laboratory, Health Sciences Faculty, University of Brasília, Brasília, DF, Brazil.
authors.forename: Ana Elizia Mascarenhas
authors.initials: AE
authors.lastname: Marques
authors.affiliation: Oral Histopathology Laboratory, Health Sciences Faculty, University of Brasília, Brasília, DF, Brazil.
authors.forename: Silvia Taveira
authors.initials: ST
authors.lastname: Elias
authors.affiliation: Department of Dentistry, Federal University of Santa Catarina, Florianópolis, SC, Brazil.|Department of Prosthodontics, Section of Orofacial Pain, Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil.
authors.forename: André Luís
authors.initials: AL
authors.lastname: Porporatti
authors.affiliation: Epithelial Biology Laboratory, Department of Periodontics and Oral Medicine, Division of Oral Pathology, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
authors.forename: Rogerio Moraes
authors.initials: RM
authors.lastname: Castilho
authors.affiliation: Epithelial Biology Laboratory, Department of Periodontics and Oral Medicine, Division of Oral Pathology, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
authors.forename: Cristiane Helena
authors.initials: CH
authors.lastname: Squarize
authors.affiliation: Department of Dentistry, Federal University of Santa Catarina, Florianópolis, SC, Brazil.|Department of Dentistry, University of Alberta, Edmonton, AB, Canada.
authors.forename: Graziela
authors.initials: G
authors.lastname: De Luca Canto
authors.affiliation: Oral Histopathology Laboratory, Health Sciences Faculty, University of Brasília, Brasília, DF, Brazil.
authors.forename: Eliete Neves Silva
authors.initials: EN
authors.lastname: Guerra
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism*; D015331:Cohort Studies; D018572:Disease-Free Survival; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D053858:Metabolic Networks and Pathways; D011379:Prognosis; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: carcinoma; head and neck cancer; mTOR pathway; prognosis; survival