Saffi Junior Mario Cezar, Duarte Ivone da Silva, Brito Rodrigo Barbosa de Oliveira, Prado Giovana Garcia, Makabe Sergio, Dellê Humberto, Camacho Cleber P
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.
Med Oncol. 2016 Nov;33(11):132. doi: 10.1007/s12032-016-0844-7. Epub 2016 Oct 19.
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.
宫颈癌（CC）是全球女性中最常见的癌症之一。人类乳头瘤病毒（HPV）与CC及其前驱病变之间的关系早在40多年前就首次受到怀疑。吲哚胺2,3-双加氧酶（IDO）是一种免疫调节酶，负责免疫系统的组织保护机制，这可能是肿瘤持续存在的关键。HPV癌蛋白E7促进细胞周期蛋白依赖性激酶抑制剂p16（CDKN2A/p16）的增加。对CDKN2A/p16 mRNA进行分离和联合分析用于CC诊断，结果很有前景。本研究的目的是评估IDO mRNA与CDKN2A/p16 mRNA之间的相关性。我们将探索两者作为诊断工具的潜力。从组织样本中提取RNA。使用高容量RNA-to-cDNA试剂盒生成cDNA。使用非线性曲线估计、ROC曲线、卡方检验、可解释的方差比例以及盖伦和甘比诺公式分析实时PCR结果。在就诊的270例患者中，对110例进行了阴道镜检查，75例进行了活检。我们发现年龄大于28岁且患有低风险病变的患者存在正相关，但在高风险病变中这种相关性消失。虽然细胞学、IDO mRNA和CDKN2A/p16 mRNA无法区分风险组，但IDO与CDKN2A/p16 mRNA联合检测结果可以区分（p = 0.028）。IDO与CDKN2A/p16 mRNA联合检测取得了最佳诊断结果，这可能会显著提高CC筛查的敏感性。
