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

11573/1680873 - 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)
Quarato, Carla Maria Irene; Dama, Elisa; Maggi, Michele; Feragalli, Beatrice; Borelli, Cristina; Del Colle, Anna; Taurchini, Marco; Maiello, Evaristo; De Cosmo, Salvatore; Lacedonia, Donato; Barbaro, Maria Pia Foschino; Carpagnano, Giovanna Elisiana; Scioscia, Giulia; Graziano, Paolo; Termine, Rosalinda; Frongillo, Elisabettamaria; Santamaria, Sonia; Venuti, Mariapia; Grimaldi, Maria Arcangela; Notarangelo, Stefano; Saponara, Annarita; Copetti, Massimiliano; Colangelo, Tommaso; Cuttano, Roberto; Macrodimitris, Dimitrios; Mazzarelli, Francesco; Talia, Michela; Mirijello, Antonio; Pazienza, Luca; Perna, Rita; Simeone, Anna; Vergara, Doriana; Varriale, Antonio; Carella, Massimo; Bianchi, Fabrizio; Sperandeo, Marco - 01a Articolo in rivista
rivista: FRONTIERS IN MEDICINE (Lausanne: Frontiers Media S.A., 2014-) pp. - - issn: 2296-858X - wos: WOS:000998597400001 (0) - scopus: 2-s2.0-85161088583 (0)

11573/1603649 - 2022 - Loss of circadian gene Timeless induces EMT and tumor progression in colorectal cancer via Zeb1-dependent mechanism
Colangelo, Tommaso; Carbone, Annalucia; Mazzarelli, Francesco; Cuttano, Roberto; Dama, Elisa; Nittoli, Teresa; Albanesi, Jacopo; Barisciano, Giovannina; Forte, Nicola; Palumbo, Orazio; Graziano, Paolo; Di Masi, Alessandra; Colantuoni, Vittorio; Sabatino, Lina; Bianchi, Fabrizio; Mazzoccoli, Gianluigi - 01a Articolo in rivista
rivista: CELL DEATH AND DIFFERENTIATION (Nature Publishing Group:Brunel Road Houndmills, Basingstoke RG21 6XS United Kingdom:011 44 20 78334000, EMAIL: institutions@natureny.com, INTERNET: http://www.nature.com, Fax: 011 44 20 78434640) pp. 1-17 - issn: 1350-9047 - wos: WOS:000742820400001 (13) - scopus: 2-s2.0-85122882056 (14)

11573/1663582 - 2022 - Extracellular vesicle microRNAs contribute to Notch signaling pathway in T-cell acute lymphoblastic leukemia
Colangelo, Tommaso; Panelli, Patrizio; Mazzarelli, Francesco; Tamiro, Francesco; Melocchi, Valentina; Palumbo, Orazio; Rossi, Giovanni; Giambra, Vincenzo; Bianchi, Fabrizio - 01a Articolo in rivista
rivista: MOLECULAR CANCER (London : BioMed Central.) pp. - - issn: 1476-4598 - wos: WOS:000903234800002 (5) - scopus: 2-s2.0-85144510172 (6)

11573/1664576 - 2022 - miRNome profiling of lung cancer metastases revealed a key role for miRNA-PD-L1 axis in the modulation of chemotherapy response
Cuttano, Roberto; Colangelo, Tommaso; Guarize, Juliana; Dama, Elisa; Cocomazzi, Maria Pia; Mazzarelli, Francesco; Melocchi, Valentina; Palumbo, Orazio; Marino, Elena; Belloni, Elena; Montani, Francesca; Vecchi, Manuela; Barberis, Massimo; Graziano, Paolo; Pasquier, Andrea; Sanz-Ortega, Julian; Montuenga, Luis M; Carbonelli, Cristiano; Spaggiari, Lorenzo; Bianchi, Fabrizio - 01a Articolo in rivista
rivista: JOURNAL OF HEMATOLOGY & ONCOLOGY (London : BioMed Central) pp. - - issn: 1756-8722 - wos: WOS:000906320400001 (2) - scopus: 2-s2.0-85145372659 (0)

11573/1672336 - 2022 - Analysis of extracellular-vesicle miRNAs in a new aggressive molecular subtype of lung cancer
Mazzarelli, Francesco; Colangelo, Tommaso; Cuttano, Roberto; Melocchi, Valentina; Dama, Elisa; Kiptiu, Patricia; Maria Perrone, Rosa; Afanga, Kuku; Bianchi, Fabrizio - 04f Poster
congresso: 7th Annual Meeting Alliance Against Cancer - Rome (Policlinico Gemelli, Roma)
libro: Alleanza Contro il Cancro (ACC) Annual Meeting - ()

11573/1672338 - 2022 - Analysis of extracellular-vesicle miRNAs in a new aggressive molecular subtype of lung cancer
Mazzarelli, Francesco; Colangelo, Tommaso; Cuttano, Roberto; Melocchi, Valentina; Dama, Elisa; Kiptiu, Patricia; Maria Perrone, Rosa; Afanga, Kuku; Bianchi, Fabrizio - 04f Poster
congresso: 62nd Annual Meeting of the Italian Cancer Society The exciting path from preclinical research to clinical application (Hotel NH Venezia Laguna Palace Viale Ancona, 2 30172 – Venezia, Italy)
libro: 62nd Annual Meeting of the Italian Cancer Society The exciting path from preclinical research to clinical application Abstract Book - ()

11573/1557095 - 2021 - Aggressive early-stage lung adenocarcinoma is characterized by epithelial cell plasticity with acquirement of stem-like traits and immune evasion phenotype
Melocchi, Valentina; Dama, Elisa; Mazzarelli, Francesco; Cuttano, Roberto; Colangelo, Tommaso; Di Candia, Leonarda; Lugli, Enrico; Veronesi, Giulia; Pelosi, Giuseppe; Ferretti, Gian Maria; Taurchini, Marco; Graziano, Paolo; Bianchi, Fabrizio - 01a Articolo in rivista
rivista: ONCOGENE (Macmillan Magazines Limited:Porters South Crinian Street, London N1 9XW United Kingdom:011 44 207 8334000, 011 44 171 8434982, Fax: 011 44 207 812358) pp. - - issn: 0950-9232 - wos: WOS:000667016100001 (7) - scopus: 2-s2.0-85108777855 (7)

11573/1488718 - 2020 - Non-coding RNAs as prognostic biomarkers: A miRNA signature specific for aggressive early-stage lung adenocarcinomas
Dama, E.; Melocchi, V.; Mazzarelli, F.; Colangelo, T.; Cuttano, R.; Candia, L. D.; Ferretti, G. M.; Taurchini, M.; Graziano, P.; Bianchi, F. - 01a Articolo in rivista
rivista: NON-CODING RNA (Basel : MDPI) pp. - - issn: 2311-553X - wos: WOS:000602247400001 (10) - scopus: 2-s2.0-85097923290 (10)

11573/1488717 - 2019 - Abstract 2582: Investigating the origin and function of circulating miRNA in lung cancer
Colangelo, Tommaso; Mazzarelli, Francesco; Cuttano, Roberto; Dama, Elisa; Melocchi, Valentina; Graziano, Paolo; Fiordelisi, Fabiola; Bianchi, Fabrizio - 04f Poster
congresso: Proceedings: AACR Annual Meeting 2019 (Atlanta)
libro: Proceedings: AACR Annual Meeting 2019 - ()

© Università degli Studi di Roma "La Sapienza" - Piazzale Aldo Moro 5, 00185 Roma