title: Leptin receptor expression and Gln223Arg polymorphism as prognostic markers in oral and oropharyngeal cancer.
abstract: The leptin gene product is released into the blood stream, passes through the blood-brain barrier, and finds the leptin receptor (LEPR) in the central nervous system. This hormone regulates food intake, hematopoiesis, inflammation, immunity, differentiation, and cell proliferation. The LEPR Gln223Arg polymorphism has been reported to alter receptor function and expression, both of which have been related with prognostics in several tumor types. Furthermore, several studies have shown a relationship between the Gln223Arg polymorphism and tumor development, and its role in oral and oropharyngeal squamous cell carcinoma is now well understood. In this study, 315 DNA samples were used for LEPR Gln223Arg genotyping and 87 primary oral and oropharyngeal squamous cell carcinomas were used for immunohistochemical expression analysis, such that a relationship between these and tumor development and prognosis could be established. Homozygous LEPR Arg223 was found to be associated with a 2-fold reduction in oral and oropharyngeal cancer risk. In contrast, the presence of the Arg223 allele in tumors was associated with worse disease-free and disease-specific survival. Low LEPR expression was found to be an independent risk factor, increasing the risk for lymph node metastasis 4-fold. In conclusion, the Gln223Arg polymorphism and LEPR expression might be valuable markers for oral and oropharyngeal cancer, suggesting that LEPR might serve as a potential target for future therapies.
authors.affiliation: Laboratório de Biologia Molecular, Hospital Heliópolis, São Paulo, SP, Brasil.
authors.forename: P R S
authors.initials: PR
authors.lastname: Rodrigues
authors.affiliation: Programa de Pós-Graduação em Biotecnologia, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.
authors.forename: L L
authors.initials: LL
authors.lastname: Maia
authors.affiliation: Escola Multicampi de Ciências Médicas do Rio Grande do Norte, Universidade Federal do Rio Grande do Norte, Caicó, RN, Brasil.
authors.forename: M
authors.initials: M
authors.lastname: Santos
authors.affiliation: Programa de Pós-Graduação em Biotecnologia, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.
authors.forename: G T
authors.initials: GT
authors.lastname: Peterle
authors.affiliation: Laboratório de Biologia Molecular, Hospital Heliópolis, São Paulo, SP, Brasil.
authors.forename: L U
authors.initials: LU
authors.lastname: Alves
authors.affiliation: Laboratório de Biologia Molecular, Hospital Heliópolis, São Paulo, SP, Brasil.
authors.forename: J T
authors.initials: JT
authors.lastname: Takamori
authors.affiliation: Instituto do Câncer, Arnaldo Vieira de Carvalho, São Paulo, SP, Brasil.
authors.forename: R P
authors.initials: RP
authors.lastname: Souza
authors.affiliation: Programa de Pós-Graduação em Biotecnologia, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.
authors.forename: W M
authors.initials: WM
authors.lastname: Barbosa
authors.affiliation: Laboratório de Biologia Molecular, Hospital Heliópolis, São Paulo, SP, Brasil.
authors.forename: A M C
authors.initials: AM
authors.lastname: Mercante
authors.affiliation: Departamento de Patologia Bucal, Faculdade de Odontologia, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: F D
authors.initials: FD
authors.lastname: Nunes
authors.affiliation: Laboratório de Biologia Molecular, Hospital Heliópolis, São Paulo, SP, Brasil.
authors.forename: M B
authors.initials: MB
authors.lastname: Carvalho
authors.affiliation: Departamento de Biologia Molecular, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, SP, Brasil.
authors.forename: E H
authors.initials: EH
authors.lastname: Tajara
authors.affiliation: Programa de Pós-Graduação em Biotecnologia, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.
authors.forename: I D
authors.initials: ID
authors.lastname: Louro
authors.affiliation: Programa de Pós-Graduação em Biotecnologia, Universidade Federal do Espírito Santo, Vitória, ES, Brasil adriana.biomol@gmail.com.
authors.forename: A M A
authors.initials: AM
authors.lastname: Silva-Conforti
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D014408:Biomarkers, Tumor / Q000235:genetics*; D001812:Blood-Brain Barrier; D015992:Body Mass Index; D005260:Female; D005838:Genotype; D006801:Humans; D020738:Leptin / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D009959:Oropharyngeal Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D054411:Receptors, Leptin / Q000235:genetics*; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; C515448:LEPR protein, human; D020738:Leptin; D054411:Receptors, Leptin