Alteration in gene expression profile of thymomas with or without myasthenia gravis linked with the nuclear factor-kappaB/autoimmune regulator pathway to myasthenia gravis pathogenesis

Thorac Cancer. 2019 Mar;10(3):564-570. doi: 10.1111/1759-7714.12980. Epub 2019 Feb 7.

Abstract

Background: To investigate the gene expression profile of a set of candidate genes for a better understanding of the molecular mechanism underlying the pathogenesis of thymoma with or without myasthenia gravis.

Methods: Thymoma patients and thymoma patients with myasthenia gravis were analyzed using microarray profiling to identify significant changes in gene expression of autoimmune regulator pathway genes including AIRE, IL-7R, CHRNA3, SYMD1, THRA, and CAV3.

Results: Across all of our samples, we found that 1484 mRNAs were upregulated and 770 were downregulated in thymoma patients compared with thymoma with myasthenia gravis patients. Gene ontology and pathway analysis revealed that a large number of genes participated in cellular functions for humoral immune response, sequence-specific DNA binding RNA polymerase II transcription factor activity, positive regulation of gene expression, regulation of neuron projection development, extracellular ligand-gated ion channel activity, positive regulation of striated muscle cell differentiation, and regulation of nuclear factor-kappaB import into the nucleus.

Conclusion: Our results revealed genetic differences between thymomas and myasthenia gravis, and identified the key candidate genes/pathways for molecular mechanism.

Keywords: Analysis; gene ontology; microarray; myasthenia gravis; pathway; thymoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIRE Protein
  • Adult
  • Autoimmune Diseases / complications
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / pathology
  • Caveolin 3 / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Male
  • Microarray Analysis
  • Middle Aged
  • Myasthenia Gravis / complications
  • Myasthenia Gravis / genetics*
  • Myasthenia Gravis / pathology
  • NF-kappa B / genetics
  • Neoplasm Proteins / genetics*
  • Receptors, Interleukin-7 / genetics
  • Receptors, Nicotinic / genetics
  • Thymoma / complications
  • Thymoma / genetics*
  • Thymoma / pathology
  • Thyroid Hormone Receptors alpha / genetics
  • Transcription Factors / genetics
  • Transcriptome / genetics*

Substances

  • CAV3 protein, human
  • Caveolin 3
  • NF-kappa B
  • Neoplasm Proteins
  • Receptors, Interleukin-7
  • Receptors, Nicotinic
  • Thyroid Hormone Receptors alpha
  • Transcription Factors
  • nicotinic receptor subunit alpha3