Dysregulation of phosphoproteins in hepatocellular carcinoma revealed via quantitative analysis of the phosphoproteome

Hepatocellular carcinoma (HCC) is one of the most frequently diagnosed types of cancer in the world. Post-translational modifications, such as phosphorylation, serve an essential role during cancer development. To identify aberrant phosphorylation in HCC, a multiplexed tandem mass tag approach combined with liquid chromatography tandem-mass spectrometry was used in the present study. The results are available via ProteomeXchange (identifier no. PXD013934). A total of 4,780 phosphorylated sites distributed on 2,209 proteins were identified and quantified, including 74 and 459 phosphorylated upregulated and downregulated proteins, respectively. Bioinformatic analysis revealed differences and similarities between HCC and normal tissues. Gene Ontology enrichment analysis provided information on biological processes, molecular functions, cellular components and sub-cellular localizations. Protein domains enrichment of differentially expressed proteins was analyzed using InterPro database. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed pathways that may potentially be involved in HCC. Integrative analysis of the functions, pathways, motifs of phosphorylated peptides, protein domains and protein interactions established a profile of the phosphoproteome of HCC, which may contribute to identify novel biomarkers for the diagnosis and prognosis of HCC, as well as novel therapeutic targets for HCC treatment.

Automated summary

This study used a multiplexed tandem mass tag approach combined with liquid chromatography tandem-mass spectrometry to analyze aberrant phosphorylation in HCC. Results revealed 4,780 phosphorylated sites on 2,209 proteins, showing differences between HCC and normal tissues and providing insights into pathways potentially involved in HCC.