The clinical characteristics and molecular mechanism of pituitary adenoma associated with meningioma

J Transl Med. 2019 Oct 29;17(1):354. doi: 10.1186/s12967-019-2103-0.

Abstract

Background: Pituitary adenoma and meningioma are the most common benign tumors in the central nervous system. Pituitary adenoma associated with meningioma (PAM) is a rare disease and the clinical features and mechanisms of PAM are unclear.

Methods: We summarized the clinical data of 57 PAM patients and compared with sporadic pituitary adenoma (SPA) and sporadic meningioma (SM). 5 pituitary adenomas of PAM and 5 SPAs were performed ceRNA microarray. qRT-PCR, Western Blot, siMEN1 and rapamycin inhibition experiment were validated for ceRNA microarray.

Results: Clinical variable analyses revealed that significant correlations between PAM and female sex as well as older age when compared with SPA and significant correlations between PAM and transitional meningioma as well as older age when compared with SM. Additionally, the characteristics of PAM were significantly different for MEN1 patients. Functional experiments showed lower expression of MEN1 can upregulate mTOR signaling, in accordance with the result of ceRNA microarray. Rapamycin treatment promotes apoptosis in primary pituitary adenoma and meningioma cells of PAM.

Conclusions: MEN1 plays an important role in PAM by upregulating mTOR signaling pathway. Rapamycin represents a potential therapeutic strategy for PAM in the future.

Keywords: Clinical characteristics; MEN1; Molecular mechanism; PAM; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / drug therapy
  • Adenoma / genetics
  • Adenoma / metabolism*
  • Adult
  • Aged
  • Apoptosis / drug effects
  • Female
  • Humans
  • Male
  • Meningeal Neoplasms / drug therapy
  • Meningeal Neoplasms / genetics
  • Meningeal Neoplasms / metabolism*
  • Meningioma / drug therapy
  • Meningioma / genetics
  • Meningioma / metabolism*
  • Metabolic Networks and Pathways
  • Middle Aged
  • Neoplasms, Multiple Primary / drug therapy
  • Neoplasms, Multiple Primary / genetics
  • Neoplasms, Multiple Primary / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Pituitary Neoplasms / drug therapy
  • Pituitary Neoplasms / genetics
  • Pituitary Neoplasms / metabolism*
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Signal Transduction
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Translational Research, Biomedical
  • Tumor Cells, Cultured
  • Young Adult

Substances

  • MEN1 protein, human
  • Proto-Oncogene Proteins
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus