High expression of high mobility group box 1 (hmgb1) predicts poor prognosis for hepatocellular carcinoma after curative hepatectomy
Menée sur 171 cas de carcinome hépatocellulaire, cette étude évalue l'association entre l'expression tumorale de la protéine HMGB1 et la survie des patients après une hépatectomie curative
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 level of HMGB1 mRNA and protein in tumor, para-tumor and normal tissue was 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 predict poorer survival only for tumor >5cm (p=0.031), but not for tumor [less than or equal to]5cm (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 >5cm.
Journal of Translational Medicine , article en libre accès, 2011