title: RAP1 GTPase overexpression is associated with cervical intraepithelial neoplasia.
abstract: RAP1 (RAS proximate 1), a small GTP-binding protein of the RAS superfamily, is a putative oncogene that is highly expressed in several malignant cell lines and types of cancers, including some types of squamous cell carcinoma. However, the participation of RAP1 in cervical carcinogenesis is unknown. We conducted a cross-sectional study of paraffin-embedded cervical biopsies to determine the association of RAP1 with cervical intraepithelial neoplasia (CIN). Standard and quantitative immunohistochemistry assessment of RAP1 expression in fixed tissue was performed on 183 paraffin-embedded cervical biopsies that were classified as normal or non-dysplastic mucosa (NDM) (n = 33); CIN grade 1 (n = 84) and CIN grade 2/3 (n = 66). A gradual increase in RAP1 expression in NDM < CIN 1 < CIN 2/3 (p<0.001) specimens was observed and was in agreement with the histopathologic diagnosis. A progressive increase in the RAP1 expression levels increased the risk of CIN 1 [odds ratio (OR) = 3.50; 95% confidence interval (CI) 1.30-10.64] 3.5 fold and the risk of CIN 2/3 (OR = 19.86, 95% CI 6.40-70.79) nearly 20 fold when compared to NDM. In addition, stereotype ordinal regression analysis showed that this progressive increase in RAP1 expression more strongly impacted CIN 2/3 than CIN 1. Our findings suggest that RAP1 may be a useful biomarker for the diagnosis of CIN.
authors: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil.
authors: Marcelo Antonio
authors: MA
authors: Pascoal-Xavier
authors: Centro de Pesquisas René Rachou/FIOCRUZ, Belo Horizonte Minas Gerais, Brasil.
authors: Anna Carolina Cançado
authors: AC
authors: Figueiredo
authors: Centro de Pesquisas René Rachou/FIOCRUZ, Belo Horizonte Minas Gerais, Brasil.
authors: Luciana Inácia
authors: LI
authors: Gomes
authors: Centro de Pesquisas René Rachou/FIOCRUZ, Belo Horizonte Minas Gerais, Brasil.
authors: Vanessa
authors: V
authors: Peruhype-Magalhães
authors: Centro de Pesquisas René Rachou/FIOCRUZ, Belo Horizonte Minas Gerais, Brasil.
authors: Carlos Eduardo
authors: CE
authors: Calzavara-Silva
authors: Departamento de Engenharia de Produção, Escola de Engenharia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil.
authors: Marcelo Azevedo
authors: MA
authors: Costa
authors: Departamento de Estatística, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil.
authors: Ilka Afonso
authors: IA
authors: Reis
authors: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil.
authors: Claudio Antônio
authors: CA
authors: Bonjardim
authors: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil.
authors: Erna Geessien
authors: EG
authors: Kroon
authors: Centro de Pesquisas René Rachou/FIOCRUZ, Belo Horizonte Minas Gerais, Brasil.
authors: Jaquelline G de
authors: JG
authors: Oliveira
authors: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil.
authors: Paulo César Peregrino
authors: PC
authors: Ferreira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D012307:Risk Factors; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D000089804:Shelterin Complex; C440809:TERF2IP protein, human; D034501:Telomere-Binding Proteins