Todeschini Paola, Salviato Elisa, Paracchini Lara, Ferracin Manuela, Petrillo Marco, Zanotti Laura, Tognon Germana, Gambino Angela, Calura Enrica, Caratti Giulia, Martini Paolo, Beltrame Luca, Maragoni Lorenzo, Gallo Daniela, Odicino Franco E, Sartori Enrico, Scambia Giovanni, Negrini Massimo, Ravaggi Antonella, D'Incalci Maurizio, Marchini Sergio, Bignotti Eliana, Romualdi Chiara
Department of Obstetrics and Gynecology, "Angelo Nocivelli" Institute of Molecular Medicine, University of Brescia, Brescia, Italy; Doctorate School of Molecular and Translational Medicine, University of Milano, Milano, Italy.
Department of Biology, University of Padova, Padova, Italy.
Cancer Lett. 2017 Mar 1;388:320-327. doi: 10.1016/j.canlet.2016.12.017. Epub 2016 Dec 22.
High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecologic neoplasm, with five-year survival rate below 30%. Early disease detection is of utmost importance to improve HGSOC cure rate. Sera from 168 HGSOC patients and 65 healthy controls were gathered together from two independent collections and stratified into a training set, for miRNA marker identification, and a validation set, for data validation. An innovative statistical approach for microarray data normalization was developed to identify differentially expressed miRNAs. Signature validation in both the training and validation sets was performed by quantitative Real Time PCR (RT-qPCR). In both the training and validation sets, miR-1246, miR-595 and miR-2278 emerged significantly over expressed in the sera of HGSOC patients compared to healthy controls. Receiver Operating Characteristic curve analysis revealed miR-1246 as the best diagnostic biomarker, with a sensitivity of 87%, a specificity of 77% and an accuracy of 84%. This study is the first step in the identification of circulating miRNAs with diagnostic relevance for HGSOC. According to its specificity and sensitivity, circulating miR-1246 levels are worthy to be further investigated as potential diagnostic biomarker for HGSOC.
高级别浆液性卵巢癌（HGSOC）是最致命的妇科肿瘤，五年生存率低于30%。早期疾病检测对于提高HGSOC治愈率至关重要。从两个独立样本中收集了168例HGSOC患者和65例健康对照者的血清，并将其分为用于鉴定miRNA标志物的训练集和用于数据验证的验证集。开发了一种用于微阵列数据标准化的创新统计方法，以鉴定差异表达的miRNA。通过定量实时PCR（RT-qPCR）在训练集和验证集中进行标志物验证。在训练集和验证集中，与健康对照相比，miR-1246、miR-595和miR-2278在HGSOC患者血清中均显著高表达。受试者工作特征曲线分析显示，miR-1246是最佳诊断生物标志物，敏感性为87%，特异性为77%，准确性为84%。本研究是鉴定与HGSOC诊断相关的循环miRNA的第一步。根据其特异性和敏感性，循环miR-1246水平作为HGSOC潜在诊断生物标志物值得进一步研究。
