Proteomic profiling of hepatocellular carcinoma in Chinese cohort reveals heat-shock proteins (Hsp27, Hsp70, GRP78) up-regulation and their associated prognostic values

Authors

  • John M. Luk Dr.,

    1. Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Hong Kong SAR, P. R. China
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  • Chi-Tat Lam,

    1. Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Hong Kong SAR, P. R. China
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  • Annie F. M. Siu,

    1. Department of Chemistry and Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, Hong Kong SAR, P. R. China
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  • Brian Y. Lam,

    1. Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Hong Kong SAR, P. R. China
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  • Irene O. L. Ng,

    Corresponding author
    1. Department of Pathology, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P. R. China
    • Department of Surgery, The University of Hong Kong, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong SAR, P. R. China Fax: +852-2819-9636
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  • Mei-Yu Hu,

    1. Experimental Research Centre, Zhongshan Hospital, Fudan University, Shanghai, P. R. China
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  • Chi-Ming Che,

    1. Department of Chemistry and Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, Hong Kong SAR, P. R. China
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  • Sheung-Tat Fan

    1. Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Hong Kong SAR, P. R. China
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Abstract

To facilitate the identification of candidate molecular biomarkers that are linked to the pathogenesis of hepatocellular carcinoma (HCC), we investigated protein-expression profiles of 146 tissue specimens including 67 pairs of tumors and adjacent non-tumors resected from HCC patients as well as 12 normal livers by 2-DE. Among the 1800 spots displayed in the liver proteome, a total of 90 protein species were found to be significantly different between the three groups (P < 0.05). Three of the top candidate markers up-regulated in HCC, with high receiver operating characteristic (ROC) curves, were identified by MS/MS analysis and belonged to the chaperone members: heat-shock protein (Hsp)27, Hsp70 and glucose-regulated protein (GRP)78. Over-expression of these chaperone proteins in HCC tissues was confirmed by Western blotting and immunohistochemistry. In correlation with clinico-pathological parameters, expression of Hsp27 was linked to α-fetoprotein level (P = 0.007) whereas up-regulation of GRP78 was associated with tumor venous infiltration (P = 0.035). No significant association of Hsp70 with any pathologic features was observed. The present HCC proteome analysis revealed that in response to the stressful cancerous microenvironment, tumor cells strived to increase the expression of chaperone proteins for cyto-protective function and to enhance tumor growth and metastasis.

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