Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, via S. Allende, 84081, Baronissi, SA, Italy.
Medical Genomics Program and Division of Oncology, AOU 'S. Giovanni di Dio e Ruggi d'Aragona' University of Salerno, Rete Oncologica Campana, 84131, Salerno, Italy.
J Transl Med. 2022 Jul 6;20(1):306. doi: 10.1186/s12967-022-03511-7.
Neuroendocrine neoplasms (NENs) represent a heterogeneous class of rare tumors with increasing incidence. They are characterized by the ability to secrete peptide hormones and biogenic amines but other reliable biomarkers are lacking, making diagnosis and identification of the primary site very challenging. While in some NENs, such as the pancreatic ones, next generation sequencing technologies allowed the identification of new molecular hallmarks, our knowledge of the molecular profile of NENs from other anatomical sites is still poor.
Starting from the concept that NENs from different organs may be clinically and genetically correlated, we applied a multi-omics approach by combining multigene panel testing, CGH-array, transcriptome and miRNome profiling and computational analyses, with the aim to highlight common molecular and functional signatures of gastroenteropancreatic (GEP)-NENs and medullary thyroid carcinomas (MTCs) that could aid diagnosis, prognosis and therapy.
By comparing genomic and transcriptional profiles, ATM-dependent signaling emerged among the most significant pathways at multiple levels, involving gene variations and miRNA-mediated regulation, thus representing a novel putative druggable pathway in these cancer types. Moreover, a set of circulating miRNAs was also selected as possible diagnostic/prognostic biomarkers useful for clinical management of NENs.
These findings depict a complex molecular and functional landscape of NENs, shedding light on novel therapeutic targets and disease biomarkers to be exploited.
神经内分泌肿瘤（NENs）是一类具有异质性的罕见肿瘤，其发病率不断上升。它们的特点是能够分泌肽类激素和生物胺，但缺乏其他可靠的生物标志物，这使得诊断和确定原发部位极具挑战性。虽然在一些 NENs 中，如胰腺 NENs，下一代测序技术允许鉴定出新的分子特征，但我们对其他解剖部位 NENs 的分子谱的了解仍然有限。
基于不同器官的 NENs 可能在临床和遗传上相关的概念，我们应用了一种多组学方法，结合了多基因panel 检测、CGH 芯片、转录组和 miRNA 谱分析以及计算分析，旨在突出胃肠胰神经内分泌肿瘤（GEP-NENs）和甲状腺髓样癌（MTCs）的共同分子和功能特征，这些特征可以辅助诊断、预后和治疗。
通过比较基因组和转录组谱，ATM 依赖性信号通路在多个水平上成为最显著的通路之一，涉及基因变异和 miRNA 介导的调节，因此代表了这些癌症类型中一种新的潜在可用药通路。此外，还选择了一组循环 miRNA 作为可能的诊断/预后生物标志物，用于 NENs 的临床管理。
这些发现描绘了 NENs 的复杂分子和功能图谱，为开发新的治疗靶点和疾病生物标志物提供了线索。
