Comparative two-dimensional polyacrylamide gel electrophoresis of the salivary proteome of children with autism spectrum disorder

J Cell Mol Med. 2015 Nov;19(11):2664-78. doi: 10.1111/jcmm.12658. Epub 2015 Aug 20.

Abstract

In the last decades, prevalence of autism spectrum disorder (ASD) has been on the rise. However, clear aetiology is still elusive and improvements in early diagnosis are needed. To uncover possible biomarkers present in ASD, we used two-dimensional polyacrylamide gel electrophoresis and nanoliquid chromatography-tandem mass spectrometry (nanoLC-MS/MS), to compare salivary proteome profiling of children with ASD and controls. A total of 889 spots were compared and only those spots with a fold change ≥1.7 and a P-value <0.05 or a fold change of ≥3.0 between ASD cases and controls were analysed by nanoLC-MS/MS. Alpha-amylase, CREB-binding protein, p532, Transferrin, Zn alpha2 glycoprotein, Zymogen granule protein 16, cystatin D and plasminogen were down-regulated in ASD. Increased expression of proto-oncogene Frequently rearranged in advanced T-cell lymphomas 1 (FRAT1), Kinesin family member 14, Integrin alpha6 subunit, growth hormone regulated TBC protein 1, parotid secretory protein, Prolactin-inducible protein precursor, Mucin-16, Ca binding protein migration inhibitory factor-related protein 14 (MRP14) was observed in individuals with ASD. Many of the identified proteins have previously been linked to ASD or were proposed as risk factors of ASD at the genetic level. Some others are involved in pathological pathways implicated in ASD causality such as oxidative stress, lipid and cholesterol metabolism, immune system disturbances and inflammation. These data could contribute to protein signatures for ASD presence, risk and subtypes, and advance understanding of ASD cause as well as provide novel treatment targets for ASD.

Keywords: 2D-PAGE; autism spectrum disorder; early diagnosis; nanoLC-MS/MS.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Autism Spectrum Disorder* / diagnosis
  • Autism Spectrum Disorder* / metabolism
  • Child
  • Electrophoresis, Gel, Two-Dimensional*
  • Humans
  • Proteome
  • Proto-Oncogene Mas
  • Salivary Proteins and Peptides / analysis*
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry*

Substances

  • MAS1 protein, human
  • Proteome
  • Proto-Oncogene Mas
  • Salivary Proteins and Peptides