Prognostic value of clinical parameters and exosomal lncRNA NEAT1_1 in MEN1-related non-functioning pancreatic neuroendocrine tumors

J Neuroendocrinol. 2025 Aug;37(8):e70024. doi: 10.1111/jne.70024. Epub 2025 Apr 2.

Abstract

Non-functioning pancreatic neuroendocrine tumors (NF-pNETs) significantly contribute to the premature death of multiple endocrine neoplasia type 1 (MEN1) patients. Reliable prognostic markers are not yet available. MicroRNAs (miRNA) and long-non-coding (lnc) RNAs, transported by extracellular vesicles, are emerging as new prognostic tools. This study aimed to analyze the clinical characteristics, the exosomal-miRNA 451 (exo-miR451) and the lnc-RNA nuclear paraspeckle assembly transcript 1 (NEAT1_1, 3.7 kB) in the mild and aggressive courses of MEN1-NFpNET disease. Patient characteristics were assessed regarding an aggressive course of disease. In addition, exo-miR451 and exo-lnc-NEAT1_1 expression levels were quantified in serum by RT-qPCR and correlated with clinical data. Immunohistochemistry results of STAT3 (signal transducer and activator of transcription 3), regulated by NEAT1, were performed in NF-pNET tissue and correlated with exo-lnc-NEAT1_1 expression. Among 66 MEN1 patients with NF-pNETs, 13 (20%) had an aggressive disease course. No significant differences in patient characteristics were observed between those with aggressive (n = 13) and mild (n = 53) disease (all p > .5). Exosomal miRNA-451 was dysregulated in 55% (n = 23) of cases, showing a trend toward higher upregulation in the aggressive group (36% vs. 19%), although this difference was not statistically significant (p = .215). Exo-NEAT1_1 was overexpressed in 42% (16/38) of patients, without significant differences between groups (p = .0523). However, exo-NEAT1_1 expression strongly correlated with STAT3 immunohistochemical staining (p = .001). Although no prognostic marker could be identified, we show for the first time that the STAT3-NEAT1 pathway plays a role in MEN1-associated NF-pNET tumorigenesis.

Keywords: STAT3; exo‐miRNA 451; extracellular vesicles; long‐non‐coding RNA NEAT1_1; multiple endocrine neoplasia type 1.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / blood
  • Exosomes* / genetics
  • Exosomes* / metabolism
  • Female
  • Humans
  • Male
  • MicroRNAs / blood
  • MicroRNAs / metabolism
  • Middle Aged
  • Multiple Endocrine Neoplasia Type 1* / diagnosis
  • Multiple Endocrine Neoplasia Type 1* / genetics
  • Multiple Endocrine Neoplasia Type 1* / metabolism
  • Neuroendocrine Tumors* / diagnosis
  • Neuroendocrine Tumors* / genetics
  • Neuroendocrine Tumors* / metabolism
  • Pancreatic Neoplasms* / blood
  • Pancreatic Neoplasms* / diagnosis
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / metabolism
  • Pancreatic Neoplasms* / pathology
  • Prognosis
  • RNA, Long Noncoding* / blood
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • STAT3 Transcription Factor / metabolism

Substances

  • RNA, Long Noncoding
  • NEAT1 long non-coding RNA, human
  • STAT3 Transcription Factor
  • Biomarkers, Tumor
  • MicroRNAs
  • STAT3 protein, human

Supplementary concepts

  • Non functioning pancreatic endocrine tumor