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Serum Extracellular Vesicle-Derived microRNAs as Potential Biomarkers for Pleural Mesothelioma in a European Prospective Study.

ABSTRACT: Malignant pleural mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Early therapeutic interventions could improve patient outcomes. We aimed to identify a pattern of microRNAs (miRNAs) as potential early non-invasive markers of MPM. In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition cohort, we screened the whole miRNome in serum extracellular vesicles (EVs) of preclinical MPM cases. In a subgroup of 20 preclinical samples collected five years prior MPM diagnosis, we observed an upregulation of miR-11400 (fold change (FC) = 2.6, adjusted p-value = 0.01), miR-148a-3p (FC = 1.5, p-value = 0.001), and miR-409-3p (FC = 1.5, p-value = 0.04) relative to matched controls. The 3-miRNA panel showed a good classification capacity with an area under the receiver operating characteristic curve (AUC) of 0.81 (specificity = 0.75, sensitivity = 0.70). The diagnostic ability of the model was also evaluated in an independent retrospective cohort, yielding a higher predictive power (AUC = 0.86). A signature of EV miRNA can be detected up to five years before MPM; moreover, the identified miRNAs could provide functional insights into the molecular changes related to the late carcinogenic process, preceding MPM development.

SUBMITTER: Casalone E

PROVIDER: S-EPMC9817828 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Serum Extracellular Vesicle-Derived microRNAs as Potential Biomarkers for Pleural Mesothelioma in a European Prospective Study.

Casalone Elisabetta E Birolo Giovanni G Pardini Barbara B Allione Alessandra A Russo Alessia A Catalano Chiara C Mencoboni Manlio M Ferrante Daniela D Magnani Corrado C Sculco Marika M Dianzani Irma I Grosso Federica F Mirabelli Dario D Filiberti Rosa Angela RA Rena Ottavio O Sacerdote Carlotta C Rodriguez-Barranco Miguel M Smith-Byrne Karl K Panico Salvatore S Agnoli Claudia C Johnson Theron T Kaaks Rudolf R Tumino Rosario R Huerta José María JM Riboli Elio E Heath Alicia K AK Trobajo-Sanmartín Camino C Schulze Matthias B MB Saieva Calogero C Amiano Pilar P Agudo Antonio A Weiderpass Elisabete E Vineis Paolo P Matullo Giuseppe G

Cancers 20221225 1

Malignant pleural mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Early therapeutic interventions could improve patient outcomes. We aimed to identify a pattern of microRNAs (miRNAs) as potential early non-invasive markers of MPM. In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition cohort, we screened the whole miRNome in serum extracellular vesicles (EVs) of preclinical MPM cases. In a subgroup of 20 preclinical samples collecte ...[more]

PMID: 36612122

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Project description:Acute rejection (AR) is a common and grave complication of liver transplantation (LT). The diagnosis of AR is challenging because it has nonspecific clinical features and requires invasive procedures. Since extracellular vesicles (EVs) are promising candidates as indicators for diagnosis of various diseases, this study aimed to identify serum EV microRNAs (miRNAs) as potential biomarkers for AR in patients subjected to LT. We collected clinical information and serum samples from the liver transplant recipients with and without AR (non-AR). EVs from the serum were isolated via ultracentrifugation and identified using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. EV RNA was extracted and sequenced on an Illumina HiSeq 2500/2000 platform to identify differentially expressed miRNAs between the groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the target gene candidates of the differentially expressed miRNAs to test their functions in biological systems. Then, we validated 12 differentially expressed miRNAs by quantitative real-time PCR. The results demonstrated that 614 EV miRNAs were significantly altered (387 up regulated and 227 down regulated) between non-AR and AR patients. GO enrichment analysis revealed that these target genes were related to cellular processes, single-organism processes, biological regulation, metabolic processes, cells, cell parts, protein-binding processes, nucleoid binding, and catalytic activity. Furthermore, KEGG pathway analysis demonstrated that the target genes of the differentially expressed miRNAs were primarily involved in ubiquitin-mediated proteolysis, lysosomes, and protein processing in the endoplasmic reticulum. miR-223 and let-7e-5p in AR patients were significantly up-regulated compared to those in non-AR patients, whereas miR-199a-3p was significantly down-regulated, which was consistent with sequencing results. The expression of serum EV miRNAs (up-regulated: miR-223 and let-7e-5p and miR-486-3p; down regulated: miR-199a-3p, miR-148a-3p and miR-152-3p) in AR patients was significantly different from that in non-AR patients, and these miRNAs can serve as promising diagnostic biomarkers for AR in patients subjected to liver transplant.

Dataset Information

Serum Extracellular Vesicle-Derived microRNAs as Potential Biomarkers for Pleural Mesothelioma in a European Prospective Study.

Publications

Serum Extracellular Vesicle-Derived microRNAs as Potential Biomarkers for Pleural Mesothelioma in a European Prospective Study.

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