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. 2014 Dec 15;14(12):e23552.
doi: 10.5812/hepatmon.23552. eCollection 2014 Dec.

Association of Upregulated HMGB1 and c-IAP2 Proteins With Hepatocellular Carcinoma Development and Progression

Man Ru Bi  1 , Li Ying Zhu  2 , Bing Zhu Yan  1 , Li Yan Chen  1 , Fu Xiang Wang  2 , Ying Ji Ma  2 , Bao Shan Yang  1
Affiliations

Association of Upregulated HMGB1 and c-IAP2 Proteins With Hepatocellular Carcinoma Development and Progression

Man Ru Bi et al. Hepat Mon. .

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most important health problems in China.

Objectives: This study analyzed expression of high-mobility group protein B1 (HMGB1) and inhibitor of apoptosis protein-2 (c-IAP2) proteins in HCC compared to paired para-tumor tissue samples to assess the association with HCC pathogenesis and progression.

Materials and methods: Sixty-eight HCC and para-tumor tissue samples were collected for Western blot, qRT-PCR and immunohistochemical analyses of HMGB1 and c-IAP2.

Results: HMGB1 and c-IAP2 proteins were highly expressed in HCC tissue samples [85.3% (58/68) and 82.4% (56/68), respectively] compared to para-tumor tissue samples [32.3% and 27.9%, respectively]. Furthermore, expression of HMGB1 was significantly associated with enhanced c-IAP2 expression in HCC tissue samples (r = 0.878, P < 0.01). Expression of HMGB1 was associated with tumor multiplicity and size, alpha-fetoprotein (AFP) level and advanced TNM stage, while expression of c-IAP2 was associated with tumor size, AFP level and advanced TNM stage.

Conclusions: Expression of HMGB1 and c-IAP2 proteins was associated with HCC development and progression, and the expression of HMGB1 and c-IAP2 proteins in HCC were significantly associated with each other. Additionally, these proteins may show promise as biomarkers to predict HCC progression.

Keywords: Biomarkers; HMGB1; Hepatocellular Carcinoma; c-IAP2 Protein.

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Figures

Figure 1.
Figure 1.. Immunohistochemical Staining of HMGB1 and c-IAP2 in HCC and Para-Tumor Tissue Samples
(A) High expression of HMGB1 in HCC tissue samples, HMGB1 immunostaining was predominantly localized in the cytoplasm of HCC cells (× 400). (B) Weak expression of HMGB1 protein in the para-tumor tissue samples ( ×400). (C) High expression of c-IAP2 protein in HCC tissue samples. c-IAP2 immunostaining mainly occurs in the cytoplasm of tumor cells (× 400). (D) Weak expression of c-IAP2 in para-tumor tissue samples (× 400).
Figure 2.
Figure 2.. Western Blot of HMGB1 and c-IAP2 in HCC and Paired Para-Tumor Tissue Samples
(A) Representative Western blot data on HMGB1 expression in cases and a chart on the relative expression levels of HMGB1 for tumor and para-tumor samples. (B) Representative Western blot data on c-IAP2 expression in cases and a chart on the relative expression levels of HMGB1 for tumor and para-tumor samples. β-actin served as an internal control. Lane T corresponds to the expression of HMGB1 and c-IAP2 in HCC samples and lane P corresponds to the expression of HMGB1 and c-IAP2 in paired para-tumor tissue samples.
Figure 3.
Figure 3.. qRT-PCR of HMGB1 and c-IAP2 mRNA in HCC and Paired Para-Tumor Tissue samples
(A) qRT-PCR analysis of HMGB1 mRNA. The expression of HMGB1 mRNA was 2.209 fold higher in HCC tissue than paired para-tumor tissue (t = 5.976, P < 0.01), (B) qRT-PCR analysis of c-IAP2 mRNA. The expression of c-IAP2 mRNA was 2.769 fold higher in tumor tissue than paired para-tumor tissue samples (t = 9.507, P < 0.01). Data are expressed as mean ± SD from three independent experiments. *** P < 0.01 compared to the para-tumor tissue samples.
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