Document Detail


Heterogeneous nuclear ribonucleoprotein A2/B1 in association with hTERT is a potential biomarker for hepatocellular carcinoma.
MedLine Citation:
PMID:  22372738     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The heterogeneous nature of hepatocellular carcinoma (HCC) and the lack of appropriate biomarkers have hampered patient prognosis and treatment stratification. To identify a new prognostic biomarker that is related to human telomerase reverse transcriptase (hTERT) in HCC, we employed a unique proteomics approach using liquid chromatograph-mass spectrometry/mass spectrometry (LC-MS/MS) after gel filtration purification of liver tissue.
METHODS: Protein lysates from HCC and cirrhotic liver tissue were subjected to gel filtration using high performance liquid chromatography. The telomerase complex was identified at a molecular mass of 350 kDa in parallel with telomerase activity. These fractionated lysates of 350 kDa were analyzed by LC-MS/MS. The relation of the identified marker and prognosis was statistically examined in surgically resected HCC patients.
RESULTS: We identified 24 differentially expressed proteins in HCC. One of these proteins, heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1), was further analyzed by immunoprecipitation assay using tissue and cell line samples and found to interact with hTERT. Moreover small interfering RNA against hnRNP A2/B1 suppressed telomerase activity, and immunohistochemical examination showed that the enhanced nuclear and cytoplasmic hnRNP A2/B1 expression in HCC was significantly associated with histological grade of tumor differentiation and microvascular invasion of HCC. Furthermore, survival analysis of 74 HCC patients who received curative surgical treatment showed that hnRNP A2/B1 expression is an independent prognostic factor for patient survival.
CONCLUSIONS: Heterogeneous nuclear ribonucleoprotein A2/B1, an hTERT-associated protein, is a potential prognostic biomarker for HCC patients and might be a therapeutic target of HCC.
Authors:
Hideki Mizuno; Masao Honda; Takayoshi Shirasaki; Taro Yamashita; Tatsuya Yamashita; Eishiro Mizukoshi; Shuichi Kaneko
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Publication Detail:
Type:  Journal Article     Date:  2012-02-28
Journal Detail:
Title:  Liver international : official journal of the International Association for the Study of the Liver     Volume:  32     ISSN:  1478-3231     ISO Abbreviation:  Liver Int.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-03     Completed Date:  2012-12-07     Revised Date:  2013-02-02    
Medline Journal Info:
Nlm Unique ID:  101160857     Medline TA:  Liver Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1146-55     Citation Subset:  IM    
Copyright Information:
© 2012 John Wiley & Sons A/S.
Affiliation:
Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
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MeSH Terms
Descriptor/Qualifier:
Carcinoma, Hepatocellular / diagnosis*,  metabolism,  mortality
Female
Heterogeneous-Nuclear Ribonucleoprotein Group A-B / genetics,  metabolism*
Humans
Liver Cirrhosis / diagnosis,  metabolism
Liver Neoplasms / diagnosis*,  metabolism,  mortality
Male
Middle Aged
Prognosis
RNA, Small Interfering / pharmacology
Telomerase / genetics,  metabolism*
Tumor Markers, Biological / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Heterogeneous-Nuclear Ribonucleoprotein Group A-B; 0/RNA, Small Interfering; 0/Tumor Markers, Biological; 0/hnRNP A2; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase

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