MicroRNA signature and integrative omics analyses define prognostic clusters and key pathways driving prognosis in patients with neuroendocrine neoplasms

Autor: Beatriz Soldevilla, Alberto Lens‐Pardo, Paula Espinosa‐Olarte, Carlos Carretero‐Puche, Sonia Molina‐Pinelo, Carlos Robles, Marta Benavent, Lourdes Gomez‐Izquierdo, Marta Fierro‐Fernández, Patricia Morales‐Burgo, Paula Jimenez‐Fonseca, Beatriz Anton‐Pascual, Yolanda Rodriguez‐Gil, Ana Teijo‐Quintans, Anna La Salvia, Beatriz Rubio‐Cuesta, Maria C. Riesco‐Martínez, Rocio Garcia‐Carbonero
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Molecular Oncology, Vol 17, Iss 4, Pp 582-597 (2023)
Druh dokumentu: article
ISSN: 1878-0261
1574-7891
DOI: 10.1002/1878-0261.13393
Popis: Neuroendocrine neoplasms (NENs) are mutationally quiet (low number of mutations/Mb), and epigenetic mechanisms drive their development and progression. We aimed at comprehensively characterising the microRNA (miRNA) profile of NENs, and exploring downstream targets and their epigenetic modulation. In total, 84 cancer‐related miRNAs were analysed in 85 NEN samples from lung and gastroenteropancreatic (GEP) origin, and their prognostic value was evaluated by univariate and multivariate models. Transcriptomics (N = 63) and methylomics (N = 30) were performed to predict miRNA target genes, signalling pathways and regulatory CpG sites. Findings were validated in The Cancer Genome Atlas cohorts and in NEN cell lines. We identified a signature of eight miRNAs that stratified patients in three prognostic groups (5‐year survival of 80%, 66% and 36%). Expression of the eight‐miRNA gene signature correlated with 71 target genes involved in PI3K–Akt and TNFα–NF‐kB signalling. Of these, 28 were associated with survival and validated in silico and in vitro. Finally, we identified five CpG sites involved in the epigenetic regulation of these eight miRNAs. In brief, we identified an 8‐miRNA signature able to predict survival of patients with GEP and lung NENs, and identified genes and regulatory mechanisms driving prognosis in NEN patients.
Databáze: Directory of Open Access Journals
Externí odkaz: