RESUMEN
Prostate cancer is a global biological, medical, and social issue aggravated by the lack of reliable, highly specific, and sensitive non-invasive tests for diagnosis and staging of prostate cancer. One prospective source of biomarkers are the cell-free miRNAs present in various biological fluids. In the present study, we validated the diagnostic potential of cell-free miRNAs: miR-19b, miR-22, miR-92a, miR-378, miR-425, miR-30e, miR-31, miR-125b, miR-200b, miR-205, miR-375, and miR-660; we estimated the required sample size and the minimal miRNA set for a subsequent large-scale validation study. Relative expression of 12 miRNA combined in 31 ratios was investigated in three fractions of biological fluids (urine extracellular vesicles, clarified urine, and plasma) obtained from patients with prostate cancer (n = 10), benign prostate hyperplasia (n = 8), and healthy volunteers (n = 11). Eight of the miRNAs found in urine vesicles (miR-19b, miR-30e, miR-31, miR-92a, miR-125, miR-200, miR-205, and miR-660) showed great promise and when combined into six ratios (miR-125b/miR-30e, miR-200/miR-30e, miR-205/miR-30e, miR-31/miR-30e, miR-660/miR-30e, and miR-19b/miR-92a) could classify patients with prostate cancer, benign prostate hyperplasia, and healthy donors with 100% specificity, 100% sensitivity, and with a high degree of reliability for most donors.
RESUMEN
Lung cancer is one of major cancers, and survival of lung cancer patients is dictated by the timely detection and diagnosis. Cell-free circulating miRNAs were proposed as candidate biomarkers for lung cancer. These RNAs are frequently deregulated in lung cancer and can persist in bodily fluids for extended periods of time, shielded from degradation by membrane vesicles and biopolymer complexes. To date, several groups reported the presence of lung tumour-specific subsets of miRNAs in blood. Here we describe the profiling of blood plasma miRNAs in lung cancer patients, healthy individuals and endobronchitis patients using miRCURY LNA miRNA qPCR Serum/Plasma Panel (Exiqon). From 241 ratios differently expressed between cancer patients and healthy individuals 19 miRNAs were selected for verification using the same platform. LASSO-penalized logistic regression model, including 10 miRNA ratios comprised of 14 individual miRNAs discriminated lung cancer patients from both control groups with AUC of 0.979.
Asunto(s)
Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/genética , MicroARNs/sangre , Anciano , Biomarcadores de Tumor/sangre , Ácidos Nucleicos Libres de Células/genética , MicroARN Circulante/sangre , MicroARN Circulante/genética , Detección Precoz del Cáncer/métodos , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Masculino , MicroARNs/biosíntesis , MicroARNs/genética , Persona de Mediana Edad , TranscriptomaRESUMEN
Lung cancer is a complex disease that often manifests at the point when treatment is not effective. Introduction of blood-based complementary diagnostics using molecular markers may enhance early detection of this disease and help reduce the burden of lung cancer. Here we evaluated the diagnostic potential of seven plasma miRNA biomarkers (miR-21, -19b, -126, -25, -205, -183, -125b) by quantitative reverse transcription PCR. Influence clinical and demographical characteristics, including age, tumor stage and cancer subtype on miRNA levels was investigated. Four miRNAs were significantly dysregulated (miR-19b, -21, -25, -183) in lung cancer patients. Combination of miR-19b and miR-183 provided detection of lung cancer with 94.7% sensitivity and 95.2% specificity (AUC = 0.990). Thus, miRNAs have shown the potential to discriminate histological subtypes of lung cancer and reliably distinguish lung cancer patients from healthy individuals.