» Articles » PMID: 22747650

High Expression of High Mobility Group Box 1 (hmgb1) Predicts Poor Prognosis for Hepatocellular Carcinoma After Curative Hepatectomy

Overview
Journal J Transl Med
Publisher Biomed Central
Date 2012 Jul 4
PMID 22747650
Citations 29
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

Assessment of combined serum sST2 and AFP levels in the diagnosis of hepatocellular carcinoma.

Tang X, Wang D, Ding T, Lin R, He M, Wang R PeerJ. 2024; 12:e18142.

PMID: 39677962 PMC: 11639131. DOI: 10.7717/peerj.18142.


Molecular determinants of immunogenic cell death elicited by radiation therapy.

Galassi C, Klapp V, Yamazaki T, Galluzzi L Immunol Rev. 2023; 321(1):20-32.

PMID: 37679959 PMC: 11075037. DOI: 10.1111/imr.13271.


HMGB1-mediated elevation of KLF7 facilitates hepatocellular carcinoma progression and metastasis through upregulating TLR4 and PTK2.

Feng W, Chen J, Huang W, Wang G, Chen X, Duan L Theranostics. 2023; 13(12):4042-4058.

PMID: 37554278 PMC: 10405848. DOI: 10.7150/thno.84388.


A murine cellular model of necroinflammation displays RAGE-dependent cytokine induction that connects to hepatoma cell injury.

Bachmann M, Lamprecht L, Gonther S, Pfeilschifter J, Muhl H J Cell Mol Med. 2020; 24(18):10356-10366.

PMID: 32697038 PMC: 7521286. DOI: 10.1111/jcmm.15649.


microRNA-548b suppresses aggressive phenotypes of hepatocellular carcinoma by directly targeting high-mobility group box 1 mRNA.

Yun Z, Meng F, Jiang P, Yue M, Li S Cancer Manag Res. 2019; 11:5821-5834.

PMID: 31417317 PMC: 6601050. DOI: 10.2147/CMAR.S198615.


References
1.
Stros M, Ozaki T, Bacikova A, Kageyama H, Nakagawara A . HMGB1 and HMGB2 cell-specifically down-regulate the p53- and p73-dependent sequence-specific transactivation from the human Bax gene promoter. J Biol Chem. 2001; 277(9):7157-64. DOI: 10.1074/jbc.M110233200. View

2.
Tafani M, Schito L, Pellegrini L, Villanova L, Marfe G, Anwar T . Hypoxia-increased RAGE and P2X7R expression regulates tumor cell invasion through phosphorylation of Erk1/2 and Akt and nuclear translocation of NF-{kappa}B. Carcinogenesis. 2011; 32(8):1167-75. DOI: 10.1093/carcin/bgr101. View

3.
Jiang W, Wang Z, Li X, Fan X, Duan Y . High-mobility group box 1 is associated with clinicopathologic features in patients with hepatocellular carcinoma. Pathol Oncol Res. 2011; 18(2):293-8. DOI: 10.1007/s12253-011-9442-3. View

4.
Liang H, Zhong Y, Zhou S, Peng L . Knockdown of RAGE expression inhibits colorectal cancer cell invasion and suppresses angiogenesis in vitro and in vivo. Cancer Lett. 2011; 313(1):91-8. DOI: 10.1016/j.canlet.2011.08.028. View

5.
Bruix J, Boix L, Sala M, Llovet J . Focus on hepatocellular carcinoma. Cancer Cell. 2004; 5(3):215-9. DOI: 10.1016/s1535-6108(04)00058-3. View