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

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

Description

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.

Sujets

• Hepatocellular carcinoma
• Hepatectomy
• Prognosis

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 5
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

Liuet al. Journal of Translational Medicine2012,10:135 http://www.translationalmedicine.com/content/10/1/135

R E S E A R C H

Open Access

High expression of high mobility group box (hmgb1) predicts poor prognosis for hepatocellular carcinoma after curative hepatectomy 1,2 1,2 1,2 1,2 1,2 1,2* Furong Liu , Yaojun Zhang , Zhenwei Peng , Hengjun Gao , Li Xu and Minshan Chen

1

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 (pand advanced TNM stage (= 0.035) pMultivariate= 0.036). 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 (pHR = 1.622, = 0.018, 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 (pbut not for tumor= 0.031), ≤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. Keywords:High mobility group box 1, Hepatocellular carcinoma, Hepatectomy, Prognosis, Prognostic factor

* Correspondence: [e-mail] 1 Department of Hepatobiliary Surgery, Cancer Centre of Sun YatSen University, 651 Dongfeng Road East, Guangzhou 510060, China 2 State Key Laboratory of Oncology in Southern China, Guangzhou 510060, China

© 2012 Liu et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.