Buzatto Adriana Zardini, de Oliveira Silva Mariana, Poppi Ronei Jesus, Simionato Ana Valéria Colnaghi
Department of Analytical Chemistry, Institute of Chemistry, University of Campinas, P.O. Box 6154, 13083-970, Campinas, São Paulo, Brazil.
National Institute of Science and Technology for Bioanalytics, Institute of Chemistry, University of Campinas, P.O. Box 6154, 13083-970, Campinas, São Paulo, Brazil.
Anal Bioanal Chem. 2017 May;409(13):3289-3297. doi: 10.1007/s00216-017-0297-7. Epub 2017 Mar 25.
Cancer is responsible for millions of deaths worldwide, but most base diseases may be cured if detected early. Screening tests may be used to identify early-stage malignant neoplasms. However, the major screening tool for prostate cancer, the prostate-specific antigen test, has unsuitable sensitivity. Since cancer cells may affect the pattern of consumption and excretion of nucleosides, such biomolecules are putative biomarkers that can be used for diagnosis and treatment evaluation. Using a previously validated method for the analysis of nucleosides in blood serum by capillary electrophoresis with UV-vis spectroscopy detection, we investigated 60 samples from healthy individuals and 42 samples from prostate cancer patients. The concentrations of nucleosides in both groups were compared and a multivariate partial least squares-discriminant analysis classification model was optimized for prediction of prostate cancer. The validation of the model with an independent sample set resulted in the correct classification of 82.4% of the samples, with sensitivity of 90.5% and specificity of 76.7%. A significant downregulation of 5-methyluridine and inosine was observed, which can be indicative of the carcinogenic process. Therefore, such analytes are potential candidates for prostate cancer screening. Graphical Abstract Separation of the studied nucleosides and the internal standard 8-Bromoguanosine by CE-UV (a); classification of the external validation samples (30 from healthy volunteers and 21 from prostate cancer patients) by the developed Partial Least Square - Discriminant Analysis (PLS-DA) model with accuracy of 82.4% (b); Receiver Operating Characteristics (ROC) curve (c); and Variable Importance in the Projection (VIP) values for the studied nucleosides (d). A significant down-regulation of 5- methyluridine (5mU) and inosine (I) was observed, which can be indicative of the presence of prostate tumors.
癌症在全球范围内导致数百万人死亡,但大多数基础疾病如果早期发现可能会被治愈。筛查测试可用于识别早期恶性肿瘤。然而,前列腺癌的主要筛查工具——前列腺特异性抗原检测,其灵敏度并不理想。由于癌细胞可能会影响核苷的消耗和排泄模式,这些生物分子是可用于诊断和治疗评估的潜在生物标志物。我们使用一种先前经过验证的方法,即通过毛细管电泳结合紫外可见光谱检测来分析血清中的核苷,对60份健康个体样本和42份前列腺癌患者样本进行了研究。比较了两组核苷的浓度,并优化了一个多变量偏最小二乘判别分析分类模型以预测前列腺癌。用一个独立样本集对该模型进行验证,结果82.4%的样本被正确分类,灵敏度为90.5%,特异性为76.7%。观察到5-甲基尿苷和肌苷有显著下调,这可能表明致癌过程。因此,这些分析物是前列腺癌筛查的潜在候选物。图形摘要 通过毛细管电泳-紫外检测分离所研究的核苷和内标8-溴鸟苷(a);用开发的偏最小二乘判别分析(PLS-DA)模型对外部验证样本(30份来自健康志愿者,21份来自前列腺癌患者)进行分类,准确率为82.4%(b);受试者工作特征(ROC)曲线(c);以及所研究核苷的投影变量重要性(VIP)值(d)。观察到5-甲基尿苷(5mU)和肌苷(I)有显著下调,这可能表明存在前列腺肿瘤。