Published July 6, 2022
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Identification of functional pathways and molecular signatures in neuroendocrine neoplasms by multi-omics analysis.

Creators

  • 1. 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.
  • 2. 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.
  • 3. Genome Research Center for Health, 84081, Baronissi, SA, Italy.
  • 4. IRCCS Synlab SDN s.p.a, Via Gianturco 113, 80143, Naples, Italy.
  • 5. Scientific Institute for Research, Hospitalization and Healthcare
  • 6. Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, 84081, Baronissi, SA, Italy.
  • 7. Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy.
  • 8. University of Padua
  • 9. MeriGen Diagnostic & c sas, traversa M. Pietravalle 11, 80131, Naples, Italy.
  • 10. Pathology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Via Mariano Semmola, 80131, Naples, Italy.
  • 11. Sarcomas and Rare Tumors Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Via Mariano Semmola, 80131, Naples, Italy.
  • 12. Department of Clinical Medicine and Surgery, Endocrinology Unit, Federico II University, Naples, Italy.
  • 13. UNESCO Chair for Health Education and Sustainable Development, Federico II University, Naples, Italy.
  • 14. 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. aweisz@unisa.it.
  • 15. 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. aweisz@unisa.it.
  • 16. Genome Research Center for Health, 84081, Baronissi, SA, Italy. aweisz@unisa.it.
  • 17. 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. rtarallo@unisa.it.
  • 18. 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. rtarallo@unisa.it.
  • 19. Genome Research Center for Health, 84081, Baronissi, SA, Italy. rtarallo@unisa.it.

Description

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. © 2022. The Author(s).
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