FRANCESCO MAZZARELLI

Dottore di ricerca

ciclo: XXXV


supervisore: Prof. Rodolfo Negri
relatore: Dr. Ugo Cavallaro
co-supervisore: Dr. Fabrizio Bianchi

Titolo della tesi: In-depth characterization of a novel aggressive subtype of lung cancer and dissection of exosomal-miRNAs as key-players for early identification

Lung adenocarcinoma (LUAD) is the most common type of non-small-cell lung cancer, and a subset of patients with early-stage LUAD experience relapses and adverse prognosis. Here we identified by a 10-gene prognostic signature an aggressive LUAD subtype, named C1, that is characterized by loss of lung cell lineage and gain of stem cell-like characteristics, along with mutator and immune evasion phenotypes. In addition, with a multi-tiered approach using coupled RNA-seq and miRNA-seq data analysis of a large cohort of lung cancer patients, we found high accuracy in scoring aggressive disease and identified a minimal signature of 7-miRNAs, which we validated in a cohort of FFPE lung adenocarcinoma samples. The results demonstrate the reliability of miRNA-based biomarkers for lung cancer prognostication and make a step forward to the application of miRNA biomarkers in the clinical routine. In line with this, we finally identified a 6-exo-miRNA signature derived from LUAD patients exosomes that is a reliable biomarker to identify the C1-LUAD subtype. Moreover, we also showed that miR-223-3p was significantly enriched in exosomes derived from C1-like cells and acted as a modulator of immune response. Overall, we provide new insights into the molecular and biological features of aggressive C1-LUAD, providing new biomarkers for the early identification of aggressive subtypes of lung cancer.

Produzione scientifica

  • 11573/1680874 - 2023 - In-depth characterization of a novel aggressive subtype of lung cancer and dissection of exosomal-miRNAs as key-players for early identification (07a Tesi di Dottorato)
    MAZZARELLI, FRANCESCO
  • 11573/1680873 - 2023 - Thoracic ultrasound combined with low-dose computed tomography may represent useful screening strategy in highly exposed population in the industrial city of Taranto (Italy) (01a Articolo in rivista)
    GRAZIANO, PAOLO; MAZZARELLI, FRANCESCO; BIANCHI, FABRIZIO
  • 11573/1488717 - 2019 - Abstract 2582: Investigating the origin and function of circulating miRNA in lung cancer (04f Poster)
    MAZZARELLI, FRANCESCO; GRAZIANO, PAOLO; BIANCHI, FABRIZIO
  • 11573/1557095 - 2021 - Aggressive early-stage lung adenocarcinoma is characterized by epithelial cell plasticity with acquirement of stem-like traits and immune evasion phenotype (01a Articolo in rivista)
    MAZZARELLI, FRANCESCO; BIANCHI, FABRIZIO
  • 11573/1488718 - 2020 - Non-coding RNAs as prognostic biomarkers: A miRNA signature specific for aggressive early-stage lung adenocarcinomas (01a Articolo in rivista)
    MAZZARELLI, FRANCESCO; BIANCHI, FABRIZIO
  • 11573/1603649 - 2022 - Loss of circadian gene Timeless induces EMT and tumor progression in colorectal cancer via Zeb1-dependent mechanism (01a Articolo in rivista)
    MAZZARELLI, FRANCESCO; COLANTUONI, VITTORIO; BIANCHI, FABRIZIO
  • 11573/1664576 - 2022 - miRNome profiling of lung cancer metastases revealed a key role for miRNA-PD-L1 axis in the modulation of chemotherapy response (01a Articolo in rivista)
    MAZZARELLI, FRANCESCO; BELLONI, ELENA; VECCHI, MANUELA; GRAZIANO, PAOLO; BIANCHI, FABRIZIO
  • 11573/1672338 - 2022 - Analysis of extracellular-vesicle miRNAs in a new aggressive molecular subtype of lung cancer (04f Poster)
    MAZZARELLI, FRANCESCO; BIANCHI, FABRIZIO
  • 11573/1672336 - 2022 - Analysis of extracellular-vesicle miRNAs in a new aggressive molecular subtype of lung cancer (04f Poster)
    MAZZARELLI, FRANCESCO; BIANCHI, FABRIZIO
  • 11573/1663582 - 2022 - Extracellular vesicle microRNAs contribute to Notch signaling pathway in T-cell acute lymphoblastic leukemia (01a Articolo in rivista)
    MAZZARELLI, FRANCESCO; BIANCHI, FABRIZIO

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