ELENA SPLENDIANI

Dottoressa di ricerca

ciclo: XXXV


supervisore: Prof.ssa Alessandra Vacca
co-supervisore: Prof.ssa Isabella Screpanti

Titolo della tesi: A novel microRNA signature for the detection of melanoma by liquid biopsy

Advanced stages of melanoma, characterized by metastatic processes, are associated with high mortality and morbidity, mainly due to rapid dissemination of the disease and the heterogeneous and not durable responses to current therapies. Diagnosis, patient stratification and monitoring are clinical needs that could be addressed by the identification of disease onset and relapse biomarkers. Indeed, research for more reliable non-invasive biomarkers in metastatic melanoma is still underway. MicroRNAs, small non-coding RNAs involved in gene regulation, are emerging as effective tools for diagnosis and monitoring of patients with cancer diseases. Here, we aimed to identify a melanoma-specific circulating microRNA signature and assess its value as a diagnostic tool. The study design consisted of one discovery and two validation phases. In the discovery phase, circulating plasma extracellular vesicles (pEV) associated microRNAs profiles were obtained from a discovery cohort of metastatic melanoma patients and normal subjects, used as controls. A pEV-microRNA signature was obtained using a LASSO penalized logistic regression model. The pEV-microRNA signature was subsequently validated both in a publicly available dataset and in an independent internal cohort. A melanoma-specific circulating microRNAs panel was thus identified and validated in three independent cohorts that presented high accuracy in differentiating melanoma patients from healthy subjects, and ROC analysis showed high specificity and sensitivity, with an area under the curve (AUC) of 1.00. Investigation of the function of the pEV-microRNA signature evidenced their possible immune suppressive role in melanoma patients. The results of this study demonstrate that a blood test based on circulating microRNAs can non-invasively detect melanoma, offering a novel diagnostic tool for improving standard care. Moreover, an immune suppressive role for melanoma pEV-microRNAs was revealed.

Produzione scientifica

  • 11573/1691730 - 2023 - Network analysis identifies circulating miR-155 as predictive biomarker of type 2 diabetes mellitus development in obese patients: a pilot study (01a Articolo in rivista)
    CATANZARO, GIUSEPPINA; TROCCHIANESI, SOFIA; SPLENDIANI, ELENA; MOCINI, EDOARDO; FILARDI, TIZIANA; PO, AGNESE; BESHARAT, ZEIN MERSINI; GENTILE, MARIA CRISTINA; PACI, PAOLA; MORANO, SUSANNA; MIGLIACCIO, SILVIA; FERRETTI, ELISABETTA
  • 11573/1667587 - 2023 - Extra-cellular vesicles derived from thyroid cancer cells promote the Epithelial to Mesenchymal Transition (EMT) and the transfer of malignant phenotypes through immune mediated mechanisms (01a Articolo in rivista)
    MARDENTE, STEFANIA; AVENTAGGIATO, MICHELE; SPLENDIANI, ELENA; MARI, EMANUELA; ZICARI, ALESSANDRA; CATANZARO, GIUSEPPINA; PO, AGNESE; COPPOLA, LUCIA; TAFANI, MARCO
  • 11573/1691552 - 2023 - Circulating cell-free DNA (cfDNA) in patients with medullary thyroid carcinoma is characterized by specific fragmentation and methylation changes with diagnostic value (01f Lettera, Nota)
    CITARELLA, ANNA; BESHARAT, ZEIN MERSINI; TROCCHIANESI, SOFIA; AUTILIO, TANJA MILENA; VERRIENTI, ANTONELLA; CATANZARO, GIUSEPPINA; SPLENDIANI, ELENA; SPINELLO, ZAIRA; ANGELONI, ANTONIO; DURANTE, COSIMO; PO, AGNESE; FERRETTI, ELISABETTA
  • 11573/1681989 - 2023 - Prospective validation study of a novel integrated pathway based on clinical features, MRI biomarkers and microRNAs for early detection of prostate cancer (01a Articolo in rivista)
    PECORARO, MARTINA; CATANZARO, GIUSEPPINA; BESHARAT, ZEIN MERSINI; MESSINA, EMANUELE; LASCHENA, LUDOVICA; TROCCHIANESI, SOFIA; SPLENDIANI, ELENA; SCIARRA, ALESSANDRO; CATALANO, CARLO; PACI, PAOLA; FERRETTI, ELISABETTA; PANEBIANCO, VALERIA
  • 11573/1436017 - 2020 - Chlamydia trachomatis elicits TLR3 expression but disrupts the inflammatory signaling down-modulating NFκB and IRF3 transcription factors in human Sertoli cells (01a Articolo in rivista)
    DI PIETRO, MARISA; FILARDO, SIMONE; PELLONI, MARIANNA; SPLENDIANI, ELENA; PO, AGNESE; PAOLI, DONATELLA; FERRETTI, ELISABETTA; SESSA, ROSA
  • 11573/1582144 - 2021 - Network analysis integrating microRNA expression profiling with MRI biomarkers and clinical data for prostate cancer early detection: a proof of concept study (01a Articolo in rivista)
    PANEBIANCO, VALERIA; PACI, PAOLA; PECORARO, MARTINA; BESHARAT, ZEIN MERSINI; CATANZARO, GIUSEPPINA; SPLENDIANI, ELENA; SCIARRA, ALESSANDRO; FARINA, LORENZO; CATALANO, CARLO; FERRETTI, ELISABETTA
  • 11573/1640662 - 2022 - Low molecular weight heparin -induced miRNA changes in peripheral blood mononuclear cells in pregnancies with unexplained recurrent pregnancy loss (01a Articolo in rivista)
    SPLENDIANI, ELENA; FERRETTI, ELISABETTA
  • 11573/1646426 - 2022 - {MEDB}-09. Unraveling the role of unfolded protein response in medulloblastoma cancer stem cells (01h Abstract in rivista)
    SPINELLO, ZAIRA; SPLENDIANI, ELENA; GIANGASPERO, FELICE; FERRETTI, ELISABETTA; CATANZARO, GIUSEPPINA
  • 11573/1633475 - 2022 - Identification and validation of mir-222-3p and mir-409-3p as plasma biomarkers in gestational diabetes mellitus sharing validated target genes involved in metabolic homeostasis (01a Articolo in rivista)
    FILARDI, TIZIANA; CATANZARO, GIUSEPPINA; SPLENDIANI, ELENA; TROCCHIANESI, SOFIA; BRUNELLI, ROBERTO; MORANO, SUSANNA; FERRETTI, ELISABETTA
  • 11573/1657751 - 2022 - A novel microRNA signature for the detection of melanoma by liquid biopsy (01a Articolo in rivista)
    SABATO, CLAUDIA; BESHARAT, ZEIN MERSINI; SPLENDIANI, ELENA; MASUELLI, LAURA; BATTISTELLI, CECILIA; VACCA, ALESSANDRA; CATANZARO, GIUSEPPINA; PO, AGNESE; FERRETTI, ELISABETTA
  • 11573/1649691 - 2022 - MiR-1248: a new prognostic biomarker able to identify supratentorial hemispheric pediatric low-grade gliomas patients associated with progression (01a Articolo in rivista)
    CATANZARO, GIUSEPPINA; BESHARAT, ZEIN MERSINI; SPLENDIANI, ELENA; PO, AGNESE; CHIACCHIARINI, MARTINA; CITARELLA, ANNA; GIANNO, FRANCESCA; CACCHIONE, ANTONELLA; MIELE, EVELINA; LOCATELLI, FRANCO; GIANGASPERO, FELICE; FERRETTI, ELISABETTA

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