The Expression of Hypoxia-Inducible Factor-1α in Hepatitis B Virus-Related Hepatocellular Carcinoma: Correlation with Patients' Prognosis and Hepatitis B Virus X Protein

被引：46

作者：

Xie, Huahong ^{[1
]}

Song, Jiugang ^{[1
]}

Liu, Kaige ^{[1
]}

Ji, Hongzan ^{[2
]}

Shen, Huiqin ^{[1
]}

Hu, Shengjuan ^{[1
]}

Yang, Guitao ^{[1
]}

Du, Yulei ^{[1
]}

Zou, Xue ^{[1
]}

Jin, Haifeng ^{[1
]}

Yan, Li ^{[1
]}

Liu, Jie ^{[1
]}

Fan, Daiming ^{[1
]}

机构：

[1] Fourth Mil Med Univ, State Key Lab Canc Biol, Inst Digest Dis, Xijing Hosp, Xian 710032, Peoples R China

[2] Nanjing Gen Hosp Nanjing Mil Command PLA, Dept Geriatr Gastroenterol, Nanjing 210002, Jiangsu Prov, Peoples R China

来源：

DIGESTIVE DISEASES AND SCIENCES | 2008年 / 53卷 / 12期

基金：

中国国家自然科学基金;

关键词：

Hypoxia inducible factor-1 alpha; Hepatitis B virus; Hepatocellular carcinoma; Prognosis; Hepatitis B virus X protein;

D O I：

10.1007/s10620-008-0296-9

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Hypoxia inducible factor-1 alpha (HIF-1 alpha) was well correlated with carcinogenesis and tumor progression in many kinds of cancer. In this study, high expression of HIF-1 alpha was found in 37 of the 72 (51.39%) tumor specimens, and significantly correlated with venous invasion and lymphonode invasion. Patients with high expression of HIF-1 alpha had a significantly shorter overall survival rate and disease-free survival rate than those with low expression. Multivariate analysis showed high HIF-1 alpha expression was a borderline independent factor of overall survival. HIF-1 alpha expression was also found to be significantly correlated with the expression of hepatitis B virus X protein (HBx), and over-expressed HBx upregulated HIF-1 alpha protein expression in vitro. These results suggested that HIF-1 alpha, which was partially regulated by HBx, might be a prognostic marker of HBV-related HCC patients.

引用

收藏

页码：3225 / 3233

页数：9

相关论文

共 29 条

[1] Hypoxia-inducible factor-1α is associated with angiogenesis, and expression of bFGF, PDGF-BB, and EGFR in invasive breast cancer [J].

Bos, R ;

van Diest, PJ ;

de Jong, JS ;

van der Groep, P ;

van der Valk, P ;

van der Wall, E .

HISTOPATHOLOGY, 2005, 46 (01) :31-36

[2] Prognostic prediction and treatment strategy in hepatocellular carcinoma [J].

Bruix, J ;

Llovet, JM .

HEPATOLOGY, 2002, 35 (03) :519-524

[3] Hypoxia-inducible factor-1α expression in the gastric carcinogenesis sequence and its prognostic role in gastric and gastro-oesophageal adenocarcinomas [J].

Griffiths, E. A. ;

Pritchard, S. A. ;

Valentine, H. R. ;

Whitchelo, N. ;

Bishop, P. W. ;

Ebert, M. P. ;

Price, P. M. ;

Welch, I. M. ;

West, C. M. L. .

BRITISH JOURNAL OF CANCER, 2007, 96 (01) :95-103

[4] Hypoxia stimulates proliferation of human hepatoma cells through the induction of hexokinase II expression [J].

Gwak, GY ;

Yoon, JH ;

Kim, KM ;

Lee, HS ;

Chung, JW ;

Gores, GJ .

JOURNAL OF HEPATOLOGY, 2005, 42 (03) :358-364

[5] Expression of hypoxia-inducible factor (HIF)-1α is associated with vascular endothelial growth factor expression and tumour anglogenesis in human oesophageal squamous cell carcinoma [J].

Kimura, S ;

Kitadai, Y ;

Tanaka, S ;

Kuwai, T ;

Hihara, J ;

Yoshida, K ;

Toge, T ;

Chayama, K .

EUROPEAN JOURNAL OF CANCER, 2004, 40 (12) :1904-1912

[6] Overexpression of hypoxia-inducible-factor 1α(HIF-1α) in oesophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage [J].

Kurokawa, T ;

Miyamoto, M ;

Kato, K ;

Cho, Y ;

Kawarada, Y ;

Hida, Y ;

Shinohara, T ;

Itoh, T ;

Okushiba, S ;

Kondo, S ;

Katoh, H .

BRITISH JOURNAL OF CANCER, 2003, 89 (06) :1042-1047

[7] Human hepatitis B virus X protein is a possible mediator of hypoxia-induced angiogenesis in hepatocarcinogenesis [J].

Lee, SW ;

Lee, YM ;

Bae, SK ;

Murakami, S ;

Yun, YD ;

Kim, KW .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 268 (02) :456-461

[8] Enhanced cell survival of Hep3B cells by the hepatitis B x antigen effector, URG11, is associated with upregulation of β-catenin [J].

Lian, ZR ;

Liu, J ;

Li, L ;

Li, XX ;

Clayton, M ;

Wu, MC ;

Wang, HY ;

Arbuthnot, P ;

Kew, M ;

Fan, DM ;

Feitelson, MA .

HEPATOLOGY, 2006, 43 (03) :415-424

[9] A cellular gene up-regulated by hepatitis B virus-encoded X antigen promotes hepatocellular growth and survival [J].

Lian, ZR ;

Liu, J ;

Pan, JB ;

Tufan, NLS ;

Zhu, MH ;

Arbuthnot, P ;

Kew, M ;

Clayton, AM ;

Feitelson, MA .

HEPATOLOGY, 2001, 34 (01) :146-157

[10] Dual-specificity phosphatase DUSP1 protects overactivation of hypoxia-inducible factor 1 through inactivating ERK MAPK [J].

Liu, CJ ;

Shi, YQ ;

Du, YL ;

Ning, XX ;

Liu, N ;

Huang, DW ;

Liang, J ;

Xue, Y ;

Fan, DM .

EXPERIMENTAL CELL RESEARCH, 2005, 309 (02) :410-418