2026-05-10T15:46:52Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/231082024-11-29T15:30:25Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Soldevilla, Beatriz author Lens-Pardo, Alberto author Espinosa-Olarte, Paula author Carretero-Puche, Carlos author Molina-Pinelo, Sonia author Robles, Carlos author Benavent, Marta author Gomez-Izquierdo, Lourdes author Fierro-Fernández, Marta author Morales-Burgo, Patricia author Jimenez-Fonseca, Paula author Anton-Pascual, Beatriz author Rodriguez-Gil, Yolanda author Teijo-Quintans, Ana author La Salvia, Anna author Rubio-Cuesta, Beatriz author Riesco-Martínez, Maria C author Garcia-Carbonero, Rocio author García-Carbonero, Rocio author Lens‐Pardo, Alberto author Espinosa‐Olarte, Paula author Carretero‐Puche, Carlos author Molina‐Pinelo, Sonia author Gomez‐Izquierdo, Lourdes author Fierro‐Fernández, Marta author Morales‐Burgo, Patricia author Jimenez‐Fonseca, Paula author Anton‐Pascual, Beatriz author Rodriguez‐Gil, Yolanda author Teijo‐Quintans, Ana author Rubio‐Cuesta, Beatriz author Riesco‐Martínez, Maria C. author Garcia‐Carbonero, Rocio author 2023-04 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 TNF?-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. Mol Oncol . 2023 ;17(4):582-597. 10.1002/1878-0261.13393 1878-0261 1574-7891 Molecular oncology 36795001 https://hdl.handle.net/20.500.12105/23108 MicroRNA signature and integrative omics analyses define prognostic clusters and key pathways driving prognosis in patients with neuroendocrine neoplasms