Analysis of proteome and post-translational modifications of 2-hydroxyisobutyrylation reveals the glycolysis pathway in oral adenoid cystic carcinoma

World J Surg Oncol. 2023 Sep 23;21(1):301. doi: 10.1186/s12957-023-03155-x.

Abstract

Purpose: Oral adenoid cystic carcinoma (OACC) has high rates of both local-regional recurrence and distant metastasis. The objective of this study is to investigate the impact of Khib on OACC and its potential as a targeted therapeutic intervention. EXPERIMENTAL DESIGN: We investigated the DEPs (differentially expressed proteins) and DHMPs between OACC-T and OACC-N using LC-MS/MS-based quantitative proteomics and using several bioinformatics methods, including GO enrichment analysis, KEGG pathway analysis, subcellular localization prediction, MEA (motif enrichment analysis), and PPI (protein-protein interaction networks) to illustrate how Khib modification interfere with OACC evolution.

Results: Compared OACC-tumor samples (OACC-T) with the adjacent normal samples (OACC-N), there were 3243 of the DEPs and 2011 Khib sites were identified on 764 proteins (DHMPs). DEPs and DHMPs were strongly associated to glycolysis pathway. GAPDH of K254, ENO of K228, and PGK1 of K323 were modified by Khib in OACC-T. Khib may increase the catalytic efficiency to promote glycolysis pathway and favor OACC progression.

Conclusions and clinical relevance: Khib may play a significant role in the mechanism of OACC progression by influencing the enzyme activity of the glycolysis pathway. These findings may provide new therapeutic options of OACC.

Keywords: Glycolysis pathway; Lysine 2-hydroxyisobutyrylation; Oral adenoid cystic carcinoma; Proteomics; Therapeutics.

MeSH terms

  • Carcinoma, Adenoid Cystic*
  • Chromatography, Liquid
  • Glycolysis
  • Humans
  • Protein Processing, Post-Translational
  • Proteome* / analysis
  • Proteome* / metabolism
  • Tandem Mass Spectrometry

Substances

  • Proteome