437PD - Integrative DNA methylome and miRNA transcriptome analysis for new biomarker discovery in Entero-Pancreatic Neuroendocrine Tumours (EP-NETS)

Date 11 September 2017
Event ESMO 2017 Congress
Session Endocrine and neuroendocrine tumours
Topics Neuroendocrine Cancers
Endocrine Cancers
Translational Research
Presenter Jorge Barriuso
Citation Annals of Oncology (2017) 28 (suppl_5): v142-v157. 10.1093/annonc/mdx368
Authors J. Barriuso1, A. Lamarca1, V. Heredia2, L. Guerra-Pastrian3, C. Alvarez-Escola4, J. Castell5, A. Custodio6, M. Miguel2, M. Mendiola2, J. Feliu7
  • 1Medical Oncology, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 2Translational Oncology, IdIPAZ – Hospital Universitario La Paz, Madrid/ES
  • 3Pathology, IdIPAZ – Hospital Universitario La Paz, Madrid/ES
  • 4Endocrinology, IdIPAZ – Hospital Universitario La Paz, Madrid/ES
  • 5Surgical Oncology, IdIPAZ – Hospital Universitario La Paz, Madrid/ES
  • 6Medical Oncology, IdIPAZ-Hospital Universitario la Paz, 28046 - Madrid/ES
  • 7Medical Oncology, IdIPAZ – Hospital Universitario La Paz, Madrid/ES

Abstract

Background

Several attempts to improve the knowledge about the molecular biology of EP-NETS. However, the majority of these studies rely on alterations or pattern descriptions rather than integrative analysis of the findings derived from different platforms. We aim to identify new potential biomarkers integrating the differential expression of miRNAs and DNA methylated regions.

Methods

From a series of 115 EP-NETS formalin-fixed and paraffin embedded samples, we selected 8 cases of small intestine (SI) NETS and 8 pancreatic (P) NETS based on relapse (yes vs no) trying to identify the most phenotypically different cases within these groups in our series. DNA and RNA were extracted. The methylome EPIC array was used to determine differentially methylated regions (DMRs) and a transcriptomic array was used to analyse miRNA expression. Quality check (QC) of data was ran prior to analysis. False discovery rate (FDR) was applied to correct for multiple comparisons. Chromosomal regions with differentially expressed miRNAs and DMRs were plotted to perform an integrative analysis.

Results

Sample-wise and chip-wise QC were performed. DMRs were analyzed comparing patients with or without relapse (R) in SI-NETS and PNETS. The most significant differentially methylated regions for R vs non-R in PNETS were found in chromosome (chr) 2, and in chr 1 and 2 for SI-NETS. A gene set analysis of the DMRs was performed using a FDR < 0.1. Gene sets commonly represented in SI-NETS and PNETS are within CD8 TCR pathway and endothelin pathway. None of the miRNAs maintain significance using a FDR

Conclusions

It is feasible to integrate the analysis of DMRs and miRNAs in EP-NETS. Certain areas of chr1 and 2 concentrated regions with different epigenetic regulation when compare R vs non-R. Validation of the findings is ongoing.

Clinical trial identification

Legal entity responsible for the study

IdIPAZ - Hospital Universitario La Paz

Funding

Fundación Eugenio Rodriguez Pascual Fundación Eugenio Rodríguez Pascual; Sociedad Española de Oncología Medica

Disclosure

All authors have declared no conflicts of interest.