Gel-based proteomics of liver cancer progression in rat

Jakob Albrethsen, Leah M. Miller, Phyllis M. Novikoff, Ruth H. Angeletti

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

A significant challenge in proteomics biomarker research is to identify the changes that are of highest diagnostic interest, among the many unspecific aberrations associated with disease burden and inflammation. In the present study liver tissue specimens (n = 18) from six experimental stages were collected from the resistant hepatocyte (RH) rat model of liver cancer and analyzed by 2D DIGE. The study included triplicates of regenerating liver, control "sham-operated" liver, three distinct premalignant stages and hepatomas. Out of 81 identified proteins two-thirds were differentially abundant in rat hepatomas compared to control rat liver and, secondly, the majority of proteins were also changed in precursor stages. This underscores the importance of adequate control samples in explorative cancer biomarker research. We confirm several proteomic changes previously identified in human hepatocellular carcinoma (HCC) and we identify novel candidate proteomic aberrations for further analysis in human HCC. In particular, increased levels of HSP70, HSP90, AKR1B1, AKR7A3, GCLM, ANXA5, VDBP, RGN and SULT1E1 were associated specifically with rat hepatomas, or with liver cancer progression in rat. In addition, we examine an integrated gel-based workflow for analysis of protein post-translational modifications (PTMs) and microtubule-association. We highlight differential PTM and localization of HSP60 as an interesting target for further analysis in liver cancer.

Original languageEnglish (US)
Pages (from-to)1367-1376
Number of pages10
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1814
Issue number10
DOIs
StatePublished - Oct 2011

Fingerprint

Liver Neoplasms
Liver
Proteomics
Rats
Hepatocellular Carcinoma
Gels
Post Translational Protein Processing
Two-Dimensional Difference Gel Electrophoresis
Aberrations
Workflow
Rat control
Tumor Biomarkers
Research
Microtubules
Proteins
Hepatocytes
Biomarkers
Inflammation
Association reactions
Tissue

Keywords

  • Biomarker
  • HSP60
  • Inflammation
  • Liver cancer
  • Post-translational modification
  • Proteomics

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Analytical Chemistry
  • Molecular Biology

Cite this

Gel-based proteomics of liver cancer progression in rat. / Albrethsen, Jakob; Miller, Leah M.; Novikoff, Phyllis M.; Angeletti, Ruth H.

In: Biochimica et Biophysica Acta - Proteins and Proteomics, Vol. 1814, No. 10, 10.2011, p. 1367-1376.

Research output: Contribution to journalArticle

Albrethsen, Jakob ; Miller, Leah M. ; Novikoff, Phyllis M. ; Angeletti, Ruth H. / Gel-based proteomics of liver cancer progression in rat. In: Biochimica et Biophysica Acta - Proteins and Proteomics. 2011 ; Vol. 1814, No. 10. pp. 1367-1376.
@article{6fd03c8284c6481b9b6ac1ff59fdb6f2,
title = "Gel-based proteomics of liver cancer progression in rat",
abstract = "A significant challenge in proteomics biomarker research is to identify the changes that are of highest diagnostic interest, among the many unspecific aberrations associated with disease burden and inflammation. In the present study liver tissue specimens (n = 18) from six experimental stages were collected from the resistant hepatocyte (RH) rat model of liver cancer and analyzed by 2D DIGE. The study included triplicates of regenerating liver, control {"}sham-operated{"} liver, three distinct premalignant stages and hepatomas. Out of 81 identified proteins two-thirds were differentially abundant in rat hepatomas compared to control rat liver and, secondly, the majority of proteins were also changed in precursor stages. This underscores the importance of adequate control samples in explorative cancer biomarker research. We confirm several proteomic changes previously identified in human hepatocellular carcinoma (HCC) and we identify novel candidate proteomic aberrations for further analysis in human HCC. In particular, increased levels of HSP70, HSP90, AKR1B1, AKR7A3, GCLM, ANXA5, VDBP, RGN and SULT1E1 were associated specifically with rat hepatomas, or with liver cancer progression in rat. In addition, we examine an integrated gel-based workflow for analysis of protein post-translational modifications (PTMs) and microtubule-association. We highlight differential PTM and localization of HSP60 as an interesting target for further analysis in liver cancer.",
keywords = "Biomarker, HSP60, Inflammation, Liver cancer, Post-translational modification, Proteomics",
author = "Jakob Albrethsen and Miller, {Leah M.} and Novikoff, {Phyllis M.} and Angeletti, {Ruth H.}",
year = "2011",
month = "10",
doi = "10.1016/j.bbapap.2011.05.018",
language = "English (US)",
volume = "1814",
pages = "1367--1376",
journal = "Biochimica et Biophysica Acta - Proteins and Proteomics",
issn = "1570-9639",
publisher = "Elsevier",
number = "10",

}

TY - JOUR

T1 - Gel-based proteomics of liver cancer progression in rat

AU - Albrethsen, Jakob

AU - Miller, Leah M.

AU - Novikoff, Phyllis M.

AU - Angeletti, Ruth H.

PY - 2011/10

Y1 - 2011/10

N2 - A significant challenge in proteomics biomarker research is to identify the changes that are of highest diagnostic interest, among the many unspecific aberrations associated with disease burden and inflammation. In the present study liver tissue specimens (n = 18) from six experimental stages were collected from the resistant hepatocyte (RH) rat model of liver cancer and analyzed by 2D DIGE. The study included triplicates of regenerating liver, control "sham-operated" liver, three distinct premalignant stages and hepatomas. Out of 81 identified proteins two-thirds were differentially abundant in rat hepatomas compared to control rat liver and, secondly, the majority of proteins were also changed in precursor stages. This underscores the importance of adequate control samples in explorative cancer biomarker research. We confirm several proteomic changes previously identified in human hepatocellular carcinoma (HCC) and we identify novel candidate proteomic aberrations for further analysis in human HCC. In particular, increased levels of HSP70, HSP90, AKR1B1, AKR7A3, GCLM, ANXA5, VDBP, RGN and SULT1E1 were associated specifically with rat hepatomas, or with liver cancer progression in rat. In addition, we examine an integrated gel-based workflow for analysis of protein post-translational modifications (PTMs) and microtubule-association. We highlight differential PTM and localization of HSP60 as an interesting target for further analysis in liver cancer.

AB - A significant challenge in proteomics biomarker research is to identify the changes that are of highest diagnostic interest, among the many unspecific aberrations associated with disease burden and inflammation. In the present study liver tissue specimens (n = 18) from six experimental stages were collected from the resistant hepatocyte (RH) rat model of liver cancer and analyzed by 2D DIGE. The study included triplicates of regenerating liver, control "sham-operated" liver, three distinct premalignant stages and hepatomas. Out of 81 identified proteins two-thirds were differentially abundant in rat hepatomas compared to control rat liver and, secondly, the majority of proteins were also changed in precursor stages. This underscores the importance of adequate control samples in explorative cancer biomarker research. We confirm several proteomic changes previously identified in human hepatocellular carcinoma (HCC) and we identify novel candidate proteomic aberrations for further analysis in human HCC. In particular, increased levels of HSP70, HSP90, AKR1B1, AKR7A3, GCLM, ANXA5, VDBP, RGN and SULT1E1 were associated specifically with rat hepatomas, or with liver cancer progression in rat. In addition, we examine an integrated gel-based workflow for analysis of protein post-translational modifications (PTMs) and microtubule-association. We highlight differential PTM and localization of HSP60 as an interesting target for further analysis in liver cancer.

KW - Biomarker

KW - HSP60

KW - Inflammation

KW - Liver cancer

KW - Post-translational modification

KW - Proteomics

UR - http://www.scopus.com/inward/record.url?scp=80051671361&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051671361&partnerID=8YFLogxK

U2 - 10.1016/j.bbapap.2011.05.018

DO - 10.1016/j.bbapap.2011.05.018

M3 - Article

VL - 1814

SP - 1367

EP - 1376

JO - Biochimica et Biophysica Acta - Proteins and Proteomics

JF - Biochimica et Biophysica Acta - Proteins and Proteomics

SN - 1570-9639

IS - 10

ER -