Gel-based proteomics of liver cancer progression in rat

Jakob Albrethsen; Leah M Miller; Phyllis M Novikoff; Ruth H Angeletti

doi:10.1016/j.bbapap.2011.05.018

Gel-based proteomics of liver cancer progression in rat

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

21 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 language	English
Journal	Biochimica et Biophysica Acta
Volume	1814
Issue number	10
Pages (from-to)	1367-76
Number of pages	10
ISSN	0006-3002
DOIs	https://doi.org/10.1016/j.bbapap.2011.05.018
Publication status	Published - Oct 2011
Externally published	Yes

Keywords

Animals
Carcinoma, Hepatocellular
Disease Models, Animal
Disease Progression
Humans
Liver Neoplasms
Male
Microtubule-Associated Proteins
Phosphoproteins
Proteomics
Rats
Rats, Inbred F344
Two-Dimensional Difference Gel Electrophoresis
Journal Article
Research Support, Non-U.S. Gov't

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10.1016/j.bbapap.2011.05.018

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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 = "Animals, Carcinoma, Hepatocellular, Disease Models, Animal, Disease Progression, Humans, Liver Neoplasms, Male, Microtubule-Associated Proteins, Phosphoproteins, Proteomics, Rats, Rats, Inbred F344, Two-Dimensional Difference Gel Electrophoresis, Journal Article, Research Support, Non-U.S. Gov't",

author = "Jakob Albrethsen and Miller, {Leah M} and Novikoff, {Phyllis M} and Angeletti, {Ruth H}",

year = "2011",

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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.

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KW - Carcinoma, Hepatocellular

KW - Disease Models, Animal

KW - Disease Progression

KW - Humans

KW - Liver Neoplasms

KW - Male

KW - Microtubule-Associated Proteins

KW - Phosphoproteins

KW - Proteomics

KW - Rats

KW - Rats, Inbred F344

KW - Two-Dimensional Difference Gel Electrophoresis

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.bbapap.2011.05.018

DO - 10.1016/j.bbapap.2011.05.018

M3 - Journal article

C2 - 21683810

SN - 0006-3002

VL - 1814

SP - 1367

EP - 1376

JO - Biochimica et Biophysica Acta

JF - Biochimica et Biophysica Acta

IS - 10

ER -

Gel-based proteomics of liver cancer progression in rat

Abstract

Keywords

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