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. 2012 Jul 2:10:135.
doi: 10.1186/1479-5876-10-135.

High expression of high mobility group box 1 (hmgb1) predicts poor prognosis for hepatocellular carcinoma after curative hepatectomy

Furong Liu  1 , Yaojun Zhang, Zhenwei Peng, Hengjun Gao, Li Xu, Minshan Chen
Affiliations

High expression of high mobility group box 1 (hmgb1) predicts poor prognosis for hepatocellular carcinoma after curative hepatectomy

Furong Liu et al. J Transl Med. .

Abstract

Background: High mobility group box 1(HMGB1) overexpression has been reported in a variety of human cancers. However, the role of HMGB1 in hepatocellular carcinoma (HCC) remains unclear. The aim of present study was to analyze HMGB1 protein expression in tumor, para-tumor and normal tissue and to assess its prognostic significance for HCC after curative hepatectomy.

Methods: The levels of HMGB1 mRNA and protein in tumor, para-tumor and normal tissue were evaluated in 11 HCC cases by Reverse Transcription-polymerase chain reaction (RT-PCR) and Western blot. Additionally, HMGB1 protein expression in 161 HCC was analyzed by immunohistochemistry and correlated with clinicopathological characteristics and survivals. Student's t-test, spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data.

Results: By RT-PCR and Western blot, the levels of HMGB1 mRNA and protein were significantly higher in HCC, compared to that in para-tumor (p < 0.001) and normal tissue (p < 0.001). Immunohistochemical staining revealed that high expression of HMGB1 was detected in 42.9% (69/161) HCC cases. High expression of HMGB1 was significantly associated with incomplete encapsulation (p = 0.035) and advanced TNM stage (p = 0.036). Multivariate analysis showed that high expression of HMGB1 was an independent prognostic factor for both overall (p = 0.009, HR = 1.834, 95%CI: 1.167-2.881) and disease-free survival (p = 0.018, HR = 1.622, 95%CI: 1.088-2.419), along with tumor size. Subgroup analysis revealed that high expression of HMGB1 predicted poorer overall survival only for tumor >5 cm (p = 0.031), but not for tumor ≤5 cm (p = 0.101).

Conclusions: HMGB1 protein might contribute to the malignant progression of HCC, high expression of HMGB1 predicts poor prognosis for patients with HCC after curative hepatectomy, especially for patients with tumor >5 cm.

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Figures

Figure 1
Figure 1
RT-PCR and Western blot analysis of HMGB1 expression in normal (N), para-tumor (P) and tumor tissue (T) of all 11 HCC cases fresh tissues. (a) Representative RT-PCR results of two cases, and (c) Representative Western blot results of two cases. (b) Relative quantity of HMGB1 mRNA expression, and (d) protein expression. Each value which represents the average of 11 cases expressed as the mean ± SE. Human GAPDH served as an internal control, the gray-scale comparison between HMGB1 and GAPDH was used to quantify the bands of RT-PCR and western blot results. * p < 0.001, compare to normal (N) and para-tumor (P).
Figure 2
Figure 2
Representative immunohistochemical staining of HMGB1 in tumor and para-tumor tissue. (a) Over expression of HMGB1 in tumor tissue, HMGB1 immunostaining was predominantly located in cytoplasm of tumor cells (×400); (b) Low expression of HMGB1 in para-tumor tissue (×400).
Figure 3
Figure 3
Overall and disease-free survival curves of 161 HCC cases after curative hepatectomy assessed by Kaplan–Meier analysis according to HMGB1 expression. Patients with high expression of HMGB1 were significantly associated with poorer overall survival (a, p = 0.008) and disease-free survival (b, p = 0.004).
Figure 4
Figure 4
Overall and disease-free survival curves assessed by Kaplan–Meier analysis according to HMGB1 expression and tumor size. (a) Overall survival. High expression of HMGB1 predicted poorer overall survival only for tumor >5 cm (group 3 VS group 4; p = 0.031); but not for tumor ≤5 cm (group 1 VS group 2; p = 0.101). (b) Disease-free survival. High expression of HMGB1 predict poor disease-free survival only for tumor >5 cm (group 3 VS group 4; p = 0.012); but not for tumor ≤5 cm (group 1 VS group 2; p = 0.087). Group 1, tumor ≤5 cm/ HMGB1 low expression (n = 49); group 2, tumor ≤5 cm/ HMGB1 high expression (n = 36); group 3, tumor >5 cm/ HMGB1 low expression (n = 43); group 4, tumor >5 cm/ HMGB1 high expression (n = 33).
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