Potential biomarkers and lncRNA-mRNA regulatory networks in invasive growth hormone-secreting pituitary adenomas

J Endocrinol Invest. 2021 Sep;44(9):1947-1959. doi: 10.1007/s40618-021-01510-x. Epub 2021 Feb 9.

Abstract

Purpose: Growth hormone-secreting pituitary adenomas (GH-PAs) are common subtypes of functional PAs. Invasive GH-PAs play a key role in restricting poor outcomes. The transcriptional changes in GH-PAs were evaluated.

Methods: In this study, the transcriptome analysis of six different GH-PA samples was performed. The functional roles, co-regulatory network, and chromosome location of differentially expressed (DE) genes in invasive GH-PAs were explored.

Results: Bioinformatic analysis revealed 101 DE mRNAs and 70 DE long non-coding RNAs (lncRNAs) between invasive and non-invasive GH-PAs. Functional enrichment analysis showed that epithelial cell differentiation and development pathways were suppressed in invasive GH-PAs, whereas the pathways of olfactory transduction, retinol metabolism, drug metabolism-cytochrome P450, and metabolism of xenobiotics by cytochrome P450 had an active trend. In the protein-protein interaction network, 11 main communities were characterized by cell- adhesion, -motility, and -cycle; transport process; phosphorus and hormone metabolic processes. The SGK1 gene was suggested to play a role in the invasiveness of GH-PAs. Furthermore, the up-regulated genes OR51B6, OR52E4, OR52E8, OR52E6, OR52N2, MAGEA6, MAGEC1, ST8SIA6-AS1, and the down-regulated genes GAD1-AS1 and SPINT1-AS1 were identified in the competing endogenous RNA network. The RT-qPCR results further supported the aberrant expression of those genes. Finally, the enrichment of DE genes in chromosome 11p15 and 12p13 regions were detected.

Conclusion: Our findings provide a new perspective for studies evaluating the underlying mechanism of invasive GH-PAs.

Keywords: Bioinformatics; Differentially expressed genes; Growth hormone-secreting pituitary adenoma; Long non-coding RNAs; mRNAs.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers*
  • Chromosomes, Human, Pair 11 / genetics
  • Chromosomes, Human, Pair 12 / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / genetics*
  • Growth Hormone-Secreting Pituitary Adenoma / diagnosis*
  • Growth Hormone-Secreting Pituitary Adenoma / genetics
  • Growth Hormone-Secreting Pituitary Adenoma / metabolism
  • Humans
  • Male
  • Metabolic Networks and Pathways*
  • Middle Aged
  • Pituitary Neoplasms / diagnosis*
  • Pituitary Neoplasms / metabolism
  • RNA, Long Noncoding / analysis*
  • RNA, Long Noncoding / genetics
  • RNA, Messenger / analysis*
  • RNA, Messenger / genetics
  • Smell
  • Vitamin A / metabolism
  • Xenobiotics / metabolism

Substances

  • Biomarkers
  • RNA, Long Noncoding
  • RNA, Messenger
  • Xenobiotics
  • Vitamin A
  • Cytochrome P-450 Enzyme System