Comparative mitochondrial proteomic analysis of hepatocellular carcinoma from patients

Proteomics Clin Appl. 2013 Jun;7(5-6):403-15. doi: 10.1002/prca.201100103. Epub 2013 May 17.

Abstract

Purpose: To define mitochondrial protein markers related to liver cancer.

Experimental design: Mitochondrial subproteomes of 20 patient-derived liver carcinoma and tumor-free control tissues were performed by 2DE coupled with MALDI-TOF/TOF. The altered patterns of three identified proteins were validated by Western blot and immunohistochemistry.

Results: The results showed that compared with tumor-free control samples, nine proteins were downregulated and six proteins were upregulated in carcinoma samples. The increased expression of Arg1 mRNA and protein was validated by Western blot, Q-RT-PCR, paraffin tissue microarray and immunohistochemistry. Furthermore, a literature review shows that Heat shock protein 10 (Hsp10), single-stranded DNA-binding protein (SSBP1), and peptidyl-prolyl cis-trans isomerase A (PPIA), which were identified as being increased in the tumor samples in this study, may be closely related to protein folding and translation.

Conclusions and clinical relevance: These results show that in addition to changes in the signaling pathways, such as the Ras-Raf-MEK-ERK pathway, altered mitochondrial DNA replication and protein folding in liver cancer are also worth studying further. Collectively, these results suggest that specific mitochondrial proteins are uniquely susceptible to alterations in expression and carry implications for the investigation of their potential as therapeutic and prognostic markers. Further studies focusing on these proteins will be used to predict treatment response and reverse the apoptosis resistance.

Publication types

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

MeSH terms

  • Adult
  • Arginase / genetics
  • Arginase / metabolism
  • Blotting, Western
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Chaperonin 10 / genetics
  • Chaperonin 10 / metabolism
  • Chromatography, High Pressure Liquid
  • Computational Biology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Electrophoresis, Gel, Two-Dimensional
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • MAP Kinase Signaling System
  • Male
  • Middle Aged
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Peptidylprolyl Isomerase / genetics
  • Peptidylprolyl Isomerase / metabolism
  • Protein Folding
  • Proteomics*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Chaperonin 10
  • DNA-Binding Proteins
  • Mitochondrial Proteins
  • Arginase
  • Peptidylprolyl Isomerase