Circulating cell-free and extracellular vesicles-derived microRNA as prognostic biomarkers in patients with early-stage NSCLC: results from RESTING study
Copyright policy )Circulating cell-free and extracellular vesicles-derived microRNA as prognostic biomarkers in patients with early-stage NSCLC: results from RESTING study
Abstract Background Factors to accurately stratify patients with early-stage non-small cell lung cancer (NSCLC) in different prognostic groups are still needed. This study aims to investigate 1) the prognostic potential of circulating cell-free (CF) and extracellular vesicles (EVs)-derived microRNA (miRNAs), and 2) their added value with respect to known prognostic factors (PFs). Methods The RESTING study is a multicentre prospective observational cohort study on resected stage IA-IIIA patients with NSCLC. The primary end-point was disease-free survival (DFS), and the main analyses were carried out separately for CF- and EV-miRNAs. CF- and EV-miRNAs were isolated from plasma, and miRNA-specific libraries were prepared and sequenced. To reach the study aims, three statistical models were specified: one using the miRNA data only (Model 1); one using both miRNAs and known PFs (age, gender, and pathological stage) (Model 2), and one using the PFs alone (Model 3). Five-fold cross-validation (CV) was used to assess the predictive performance of each. Standard Cox regression and elastic net regularized Cox regression were used. Results A total of 222 patients were enrolled. The median follow-up time was 26.3 (95% CI 25.4–27.6) months. From Model 1, three CF-miRNAs and 21 EV-miRNAs were associated with DFS. In Model 2, two CF-miRNAs (miR-29c-3p and miR-877-3p) and five EV-miRNAs (miR-181a-2-3p, miR-182-5p, miR-192-5p, miR-532-3p and miR-589-5p) remained associated with DFS. From pathway enrichment analysis, TGF-beta and NOTCH were the most involved pathways. Conclusion This study identified promising prognostic CF- and EV-miRNAs that could be used as a non-invasive, cost-effective tool to aid clinical decision-making. However, further evaluation of the obtained miRNAs in an external cohort of patients is warranted.
Male, Adult, CHEMICALS AND DRUGS::Biological Factors::Biomarkers::Biomarkers, Tumor, COMPUESTOS QUÍMICOS Y DROGAS::nucleótidos y nucleósidos de ácidos nucleicos::elementos antisentido (genética)::ARN antiparalelo::microARN, Lung Neoplasms, COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores::marcadores tumorales, Lung cancer, Circulating cell-free, extracellular vesicles-derived microRNA, ANATOMÍA::células::estructuras celulares::espacio extracelular::vesículas extracelulares, Extracellular Vesicles, Pulmons - Càncer, COMPUESTOS QUÍMICOS Y DROGAS::nucleótidos y nucleósidos de ácidos nucleicos::elementos antisentido (genética)::ARN antiparalelo::microARN::microARN circulante, Carcinoma, Non-Small-Cell Lung, ANATOMY::Cells::Cellular Structures::Extracellular Space::Extracellular Vesicles, Biomarkers, Tumor, Humans, CHEMICALS AND DRUGS::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs, Prospective Studies, Circulating MicroRNA, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico, RC254-282, Aged, Neoplasm Staging, MicroARN, Research, Marcadors tumorals, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Middle Aged, DISEASES::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell Lung, Prognosis, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas, MicroRNAs, CHEMICALS AND DRUGS::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs::Circulating MicroRNA, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis, Female
Male, Adult, CHEMICALS AND DRUGS::Biological Factors::Biomarkers::Biomarkers, Tumor, COMPUESTOS QUÍMICOS Y DROGAS::nucleótidos y nucleósidos de ácidos nucleicos::elementos antisentido (genética)::ARN antiparalelo::microARN, Lung Neoplasms, COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores::marcadores tumorales, Lung cancer, Circulating cell-free, extracellular vesicles-derived microRNA, ANATOMÍA::células::estructuras celulares::espacio extracelular::vesículas extracelulares, Extracellular Vesicles, Pulmons - Càncer, COMPUESTOS QUÍMICOS Y DROGAS::nucleótidos y nucleósidos de ácidos nucleicos::elementos antisentido (genética)::ARN antiparalelo::microARN::microARN circulante, Carcinoma, Non-Small-Cell Lung, ANATOMY::Cells::Cellular Structures::Extracellular Space::Extracellular Vesicles, Biomarkers, Tumor, Humans, CHEMICALS AND DRUGS::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs, Prospective Studies, Circulating MicroRNA, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico, RC254-282, Aged, Neoplasm Staging, MicroARN, Research, Marcadors tumorals, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Middle Aged, DISEASES::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell Lung, Prognosis, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas, MicroRNAs, CHEMICALS AND DRUGS::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs::Circulating MicroRNA, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis, Female
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