Circulating hsa-miR-5096 predicts 18F-FDG PET/CT positivity and modulates somatostatin receptor 2 expression: a novel miR-based assay for pancreatic neuroendocrine tumors
| العنوان: | Circulating hsa-miR-5096 predicts 18F-FDG PET/CT positivity and modulates somatostatin receptor 2 expression: a novel miR-based assay for pancreatic neuroendocrine tumors |
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| المؤلفون: | Bocchini, Martine, Tazzari, Marcella, Ravaioli, Sara, Piccinini, Filippo, Foca, Flavia, Tebaldi, Michela, Nicolini, Fabio, Grassi, Ilaria, Severi, Stefano, Calogero, Raffaele Adolfo, Arigoni, Maddalena, Schrader, Joerg, Mazza, Massimiliano, Paganelli, Giovanni |
| المساهمون: | Bocchini, Martine, Tazzari, Marcella, Ravaioli, Sara, Piccinini, Filippo, Foca, Flavia, Tebaldi, Michela, Nicolini, Fabio, Grassi, Ilaria, Severi, Stefano, Calogero, Raffaele Adolfo, Arigoni, Maddalena, Schrader, Joerg, Mazza, Massimiliano, Paganelli, Giovanni |
| المصدر: | Frontiers in Oncology. 13 |
| بيانات النشر: | Frontiers Media SA, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Cancer Research, pancreatic neuroendocrine tumors, PRRT (peptide receptor radionuclide therapy), miRNA – microRNA, functional imaging (positron-emission tomography), SSTR2, Oncology |
| الوصف: | Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) are rare diseases encompassing pancreatic (PanNETs) and ileal NETs (SINETs), characterized by heterogeneous somatostatin receptors (SSTRs) expression. Treatments for inoperable GEP-NETs are limited, and SSTR-targeted Peptide Receptor Radionuclide Therapy (PRRT) achieves variable responses. Prognostic biomarkers for the management of GEP-NET patients are required. 18F-FDG uptake is a prognostic indicator of aggressiveness in GEP-NETs. This study aims to identify circulating and measurable prognostic miRNAs associated with 18F-FDG-PET/CT status, higher risk and lower response to PRRT.MethodsWhole miRNOme NGS profiling was conducted on plasma samples obtained from well-differentiated advanced, metastatic, inoperable G1, G2 and G3 GEP-NET patients enrolled in the non-randomized LUX (NCT02736500) and LUNET (NCT02489604) clinical trials prior to PRRT (screening set, n= 24). Differential expression analysis was performed between 18F-FDG positive (n=12) and negative (n=12) patients. Validation was conducted by Real Time quantitative PCR in two distinct well-differentiated GEP-NET validation cohorts, considering the primary site of origin (PanNETs n=38 and SINETs n=30). The Cox regression was applied to assess independent clinical parameters and imaging for progression-free survival (PFS) in PanNETs. In situ RNA hybridization combined with immunohistochemistry was performed to simultaneously detect miR and protein expression in the same tissue specimens. This novel semi-automated miR-protein protocol was applied in PanNET FFPE specimens (n=9). In vitro functional experiments were performed in PanNET models.ResultsWhile no miRNAs emerged to be deregulated in SINETs, hsa-miR-5096, hsa-let-7i-3p and hsa-miR-4311 were found to correlate with 18F-FDG-PET/CT in PanNETs (p-value:18F-FDG-PET/CT positive PanNETs with worse prognosis after PRRT (p-value:68Gallium-DOTATOC captation values (p-value:SSTR2 when ectopically expressed in PanNET cells (p-value:Conclusionshsa-miR-5096 well performs as a biomarker for 18F-FDG-PET/CT and as independent predictor of PFS. Moreover, exosome-mediated delivery of hsa-miR-5096 may promote SSTR2 heterogeneity and thus resistance to PRRT. |
| وصف الملف: | ELETTRONICO |
| تدمد: | 2234-943X 0273-6500 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e34dd94105006b9bafe3f36b4eb325e4 https://doi.org/10.3389/fonc.2023.1136331 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e34dd94105006b9bafe3f36b4eb325e4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2234943X 02736500 |
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