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Correlation between indoleamine 2,3 dioxygenase mRNA and CDKN2A/p16 mRNA: a combined strategy to cervical cancer diagnosis

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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.

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Funding

No specific funding was obtained to support the conduct of this study.

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Authors and Affiliations

  1. 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

    Mario Cezar Saffi Junior, Ivone da Silva Duarte, Rodrigo Barbosa de Oliveira Brito, Giovana Garcia Prado, Humberto Dellê & Cleber P. Camacho

  2. Low Genital Tract Outpatient Clinic, Division of Gynecology of Conjunto Hospitalar do Mandaqui, São Paulo, SP, Brazil

    Mario Cezar Saffi Junior & Sergio Makabe

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  1. Mario Cezar Saffi Junior
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  2. Ivone da Silva Duarte
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  3. Rodrigo Barbosa de Oliveira Brito
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  7. Cleber P. Camacho
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Correspondence to Cleber P. Camacho.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Saffi Junior, M.C., Duarte, I.d.S., Brito, R.B.d.O. et al. Correlation between indoleamine 2,3 dioxygenase mRNA and CDKN2A/p16 mRNA: a combined strategy to cervical cancer diagnosis. Med Oncol 33, 132 (2016). https://doi.org/10.1007/s12032-016-0844-7

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  • DOI: https://doi.org/10.1007/s12032-016-0844-7

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