Quantitative proteomics reveal up-regulated protein expression of the SET complex associated with hepatocellular carcinoma.
J Proteome Res
; 11(2): 871-85, 2012 Feb 03.
Article
en En
| MEDLINE
| ID: mdl-22082227
ABSTRACT
We combined culture-derived isotope tags (CDITs) with two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) to extensively survey abnormal protein expression associated with hepatocellular carcinoma (HCC) in clinical tissues. This approach yielded an in-depth quantitated proteome of 1360 proteins. Importantly, 267 proteins were significantly regulated with a fold-change of at least 1.5. The proteins up-regulated in HCC tissues are involved in regulatory processes, such as the granzyme A-mediated apoptosis pathway (The GzmA pathway). The SET complex, a central component in the GzmA pathway, was significantly up-regulated in HCC tissue. The elevated expressions of all of the SET complex components were validated by Western blotting. Among them, ANP32A and APEX1 were further investigated by immunohistochemistry staining using tissue microarrays (59 cases), confirming their overexpression in tumors. The up-regulation and nuclear accumulations of APEX1 was associated not only with HCC malignancy but also with HCC differentiation in 96 clinical HCC cases. Our work provided a systematic and quantitative analysis and demonstrated key changes in clinical HCC tissues. These proteomic signatures could help to unveil the underlying mechanisms of hepatocarcinogenesis and may be useful for the discovery of candidate biomarkers.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
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Biomarcadores de Tumor
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Carcinoma Hepatocelular
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Proteómica
/
Chaperonas de Histonas
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Neoplasias Hepáticas
Tipo de estudio:
Qualitative_research
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Proteome Res
Asunto de la revista:
BIOQUIMICA
Año:
2012
Tipo del documento:
Article
País de afiliación:
China