Souza Marilesia Ferreira de, Kuasne Hellen, Barros-Filho Mateus de Camargo, Cilião Heloísa Lizotti, Marchi Fabio Albuquerque, Fuganti Paulo Emilio, Paschoal Alexandre Rossi, Rogatto Silvia Regina, Cólus Ilce Mara de Syllos
General Biology Department, State University of Londrina, Londrina, Paraná, Brazil.
CIPE, AC Camargo Cancer Center, São Paulo, São Paulo, Brazil.
PLoS One. 2017 Sep 14;12(9):e0184094. doi: 10.1371/journal.pone.0184094. eCollection 2017.
Circulating nucleic acids are found in free form in body fluids and may serve as minimally invasive tools for cancer diagnosis and prognosis. Only a few studies have investigated the potential application of circulating mRNAs and microRNAs (miRNAs) in prostate cancer (PCa). The Cancer Genome Atlas (TCGA) database was used for an in silico analysis to identify circulating mRNA and miRNA as potential markers of PCa. A total of 2,267 genes and 49 miRNAs were differentially expressed between normal and tumor samples. The prediction analyses of target genes and integrative analysis of mRNA and miRNA expression revealed eleven genes and eight miRNAs which were validated by RT-qPCR in plasma samples from 102 untreated PCa patients and 50 cancer-free individuals. Two genes, OR51E2 and SIM2, and two miRNAs, miR-200c and miR-200b, showed significant association with PCa. Expression levels of these transcripts distinguished PCa patients from controls (67% sensitivity and 75% specificity). PCa patients and controls with prostate-specific antigen (PSA) ≤ 4.0 ng/mL were discriminated based on OR51E2 and SIM2 expression levels. The miR-200c expression showed association with Gleason score and miR-200b, with bone metastasis, bilateral tumor, and PSA > 10.0 ng/mL. The combination of circulating mRNA and miRNA was useful for the diagnosis and prognosis of PCa.
循环核酸以游离形式存在于体液中,可作为癌症诊断和预后的微创工具。仅有少数研究探讨了循环mRNA和微小RNA(miRNA)在前列腺癌(PCa)中的潜在应用。利用癌症基因组图谱(TCGA)数据库进行计算机分析,以鉴定循环mRNA和miRNA作为PCa的潜在标志物。正常样本和肿瘤样本之间共有2267个基因和49个miRNA存在差异表达。对靶基因的预测分析以及mRNA和miRNA表达的综合分析揭示了11个基因和8个miRNA,这些在102例未经治疗的PCa患者和50例无癌个体的血浆样本中通过RT-qPCR得到验证。两个基因OR51E2和SIM2以及两个miRNA miR-200c和miR-200b与PCa显著相关。这些转录本的表达水平可区分PCa患者和对照组(敏感性67%,特异性75%)。根据OR51E2和SIM2表达水平对前列腺特异性抗原(PSA)≤4.0 ng/mL的PCa患者和对照组进行区分。miR-200c表达与Gleason评分相关,miR-200b与骨转移、双侧肿瘤以及PSA>10.0 ng/mL相关。循环mRNA和miRNA的组合对PCa的诊断和预后具有重要意义。