title: Correlation between indoleamine 2,3 dioxygenase mRNA and CDKN2A/p16 mRNA: a combined strategy to cervical cancer diagnosis.
abstract: Cervical cancer (CC) is one of the most common cancers among women worldwide. The relation of the human papillomavirus (HPV) with CC and its precursor lesions was first suspected for over 40 years. The indoleamine 2,3 dioxygenase (IDO) is an immune modulator enzyme responsible for the immune system tissue protection mechanism, which may be the key to the tumoural persistence. HPV oncoprotein E7 promotes the increase in cyclin-dependent kinase inhibitor p16 (CDKN2A/p16). The isolated and combined analysis of CDKN2A/p16 mRNA to CC diagnosis was done with promising results. The aim of this study is to evaluate the correlation between IDO mRNA and CDKN2A/p16 mRNA. We will explore the potential of both as diagnostic tools. RNA was extracted from tissue samples. cDNA was generated with High Capacity RNA-to-cDNA kit. The real-time PCR results were analysed using nonlinear curve estimation, ROC curve, Chi-squared test, the proportion of variance explained and Galen and Gambino formulas. From 270 patients attended, colposcopy examination was performed in 110 and the biopsy in 75 patients. We found a positive correlation in patients older than 28 years old with low-risk lesions, but the correlation is lost in high-risk lesions. Although cytology, IDO mRNA and CDKN2A/p16 mRNA could not differentiate the risk groups, IDO combined with CDKN2A/p16 mRNA results could (p = 0.028). The best diagnostic result was achieved by IDO coupled with CDKN2A/p16 mRNA, which may considerably increase the sensitivity of screening for CC.
authors.affiliation: Molecular Innovation and Biotechnology Laboratory, Post-Graduation Program in Medicine, Universidade Nove de Julho (UNINOVE), Rua Vergueiro, 235/249, Liberdade, São Paulo, SP, CEP: 01504-001, Brazil.|Low Genital Tract Outpatient Clinic, Division of Gynecology of Conjunto Hospitalar do Mandaqui, São Paulo, SP, Brazil.
authors.forename: Mario Cezar
authors.initials: MC
authors.lastname: Saffi Junior
authors.affiliation: Molecular Innovation and Biotechnology Laboratory, Post-Graduation Program in Medicine, Universidade Nove de Julho (UNINOVE), Rua Vergueiro, 235/249, Liberdade, São Paulo, SP, CEP: 01504-001, Brazil.
authors.forename: Ivone da Silva
authors.initials: ID
authors.lastname: Duarte
authors.affiliation: Molecular Innovation and Biotechnology Laboratory, Post-Graduation Program in Medicine, Universidade Nove de Julho (UNINOVE), Rua Vergueiro, 235/249, Liberdade, São Paulo, SP, CEP: 01504-001, Brazil.
authors.forename: Rodrigo Barbosa de Oliveira
authors.initials: RB
authors.lastname: Brito
authors.affiliation: Molecular Innovation and Biotechnology Laboratory, Post-Graduation Program in Medicine, Universidade Nove de Julho (UNINOVE), Rua Vergueiro, 235/249, Liberdade, São Paulo, SP, CEP: 01504-001, Brazil.
authors.forename: Giovana Garcia
authors.initials: GG
authors.lastname: Prado
authors.affiliation: Low Genital Tract Outpatient Clinic, Division of Gynecology of Conjunto Hospitalar do Mandaqui, São Paulo, SP, Brazil.
authors.forename: Sergio
authors.initials: S
authors.lastname: Makabe
authors.affiliation: Molecular Innovation and Biotechnology Laboratory, Post-Graduation Program in Medicine, Universidade Nove de Julho (UNINOVE), Rua Vergueiro, 235/249, Liberdade, São Paulo, SP, CEP: 01504-001, Brazil.
authors.forename: Humberto
authors.initials: H
authors.lastname: Dellê
authors.affiliation: Molecular Innovation and Biotechnology Laboratory, Post-Graduation Program in Medicine, Universidade Nove de Julho (UNINOVE), Rua Vergueiro, 235/249, Liberdade, São Paulo, SP, CEP: 01504-001, Brazil. camacho@uni9.pro.br.
authors.forename: Cleber P
authors.initials: CP
authors.lastname: Camacho
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics*; D008875:Middle Aged; D050725:Papillomavirus E7 Proteins / Q000235:genetics; D012333:RNA, Messenger; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; C059731:oncogene protein E7, Human papillomavirus type 16
keywords: CDKN2A; Cervical cancer; Cytology; IDO; Screening program; mRNA