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Increased polycomb-group oncogene Bmi-1 expression correlates with poor prognosis in hepatocellular carcinoma

  • Hui Wang
  • Ke Pan
  • Hua-kun Zhang
  • De-sheng Weng
  • Jun Zhou
  • Jian-jun Li
  • Wei Huang
  • Hai-feng Song
  • Min-shan Chen
  • Jian-chuan XiaEmail author
Original Paper

Abstract

Purpose

Recent studies have identified polycomb-group gene Bmi-1 as oncogene in the generation of mouse pre-cell lymphomas, and overexpression of Bmi-1 has been found in several human tumor with the disease progress and poor prognosis of the cancer patients.

Methods

In present study, we investigated Bmi-1 expression and its prognostic significance in hepatocellular carcinoma (HCC) by performing immunohistochemical analysis, using a total of 137 HCC clinical tissue samples.

Results

High Bmi-1 expression (Bmi-1 2+ or 3+) was shown in 29.9% cases. The positive immuno-staining of Bmi-1 was not only in well/moderately-differentiated tumor cells, but also in surrounding noncancerous or cirrhotic liver tissue. Bmi-1 expression level did not correlate with any clinicopathological parameters. However, survival analysis showed that the high-Bmi-1 group had a significantly shorter overall survival time than the low-Bmi-1 group (P = 0.047). Multivariate analysis after 24 months revealed that Bmi-1 expression was a significant and independent prognostic parameter (P = 0.002) for HCC patients.

Conclusions

Our study indicated that Bmi-1 could be a candidate biomarker for long-term survival in HCC.

Keywords

Hepatocellular carcinoma Bmi-1 Expression Immunohistochemical analysis Prognosis 

References

  1. Bosch FX, Ribes J, Cleries R, Diaz M (2005) Epidemiology of hepatocellular carcinoma. Clin Liver Dis 9:191–211PubMedCrossRefGoogle Scholar
  2. Breuer RH, Snijders PJ, Smit EF, Sutedja TG, Sewalt RG, Otte AP, van Kemenade FJ, Postmus PE, Meijer CJ, Raaphorst FM (2004) Increased expression of the EZH2 polycomb group gene in BMI-1-positive neoplastic cells during bronchial carcinogenesis. Neoplasia 6:736–743PubMedCrossRefGoogle Scholar
  3. Chowdhury M, Mihara K, Yasunaga S, Ohtaki M, Takihara Y, Kimura A (2007) Expression of Polycomb-group (PcG) protein BMI-1 predicts prognosis in patients with acute myeloid leukemia. Leukemia 21:1116–1122PubMedGoogle Scholar
  4. Cui H, Hu B, Li T, Ma J, Alam G, Gunning WT, Ding HF (2007) Bmi-1 is essential for the tumorigenicity of neuroblastoma cells. Am J Pathol 170:1370–1378PubMedCrossRefGoogle Scholar
  5. Dimri GP, Martinez JL, Jacobs JJ, Keblusek P, Itahana K, Van Lohuizen M, Campisi J, Wazer DE, Band V (2002) The Bmi-1 oncogene induces telomerase activity and immortalizes human mammary epithelial cells. Cancer Res 62:4736–4745PubMedGoogle Scholar
  6. Haupt Y, Bath ML, Harris AW, Adams JM (1993) Bmi-1 transgene induces lymphomas and collaborates with myc in tumorigenesis. Oncogene 8:3161–3164PubMedGoogle Scholar
  7. Jacobs JJ, Kieboom K, Marino S, DePinho RA, van Lohuizen M (1999a) The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus. Nature 397:164–168PubMedCrossRefGoogle Scholar
  8. Jacobs JJ, Scheijen B, Voncken JW, Kieboom K, Berns A, van Lohuizen M (1999b) Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARF. Genes Dev 13:2678–2690PubMedCrossRefGoogle Scholar
  9. Kang MK, Kim RH, Kim SJ, Yip FK, Shin KH, Dimri GP, Christensen R, Han T, Park NH (2007) Elevated Bmi-1 expression is associated with dysplastic cell transformation during oral carcinogenesis and is required for cancer cell replication and survival. Br J Cancer 96:126–133PubMedCrossRefGoogle Scholar
  10. Kim JH, Yoon SY, Jeong SH, Kim SY, Moon SK, Joo JH, Lee Y, Choe IS, Kim JW (2004a) Overexpression of Bmi-1 oncoprotein correlates with axillary lymph node metastases in invasive ductal breast cancer. Breast 13:383–388PubMedCrossRefGoogle Scholar
  11. Kim JH, Yoon SY, Kim CN, Joo JH, Moon SK, Choe IS, Choe YK, Kim JW (2004b) The Bmi-1 oncoprotein is overexpressed in human colorectal cancer and correlates with the reduced p16INK4a/p14ARF proteins. Cancer Lett 203:217–224PubMedCrossRefGoogle Scholar
  12. Llovet JM, Burroughs A, Bruix J (2003) Hepatocellular carcinoma. Lancet 362:1907–1917PubMedCrossRefGoogle Scholar
  13. Mohty M, Yang AS, Szydlo RM, Apperley JF, Melo JV (2007) The polycomb group BMI-1 gene is a molecular marker for predicting prognosis of chronic myeloid leukemia. Blood 110:380–383PubMedCrossRefGoogle Scholar
  14. Neo SY, Leow CK, Vega VB, Long PM, Islam AF, Lai PB, Liu ET, Ren EC (2004) Identification of discriminators of hepatoma by gene expression profiling using a minimal dataset approach. Hepatology 39:944–953PubMedCrossRefGoogle Scholar
  15. Okuda K (2000) Hepatocellular carcinoma. J Hepatol 32:225–237PubMedCrossRefGoogle Scholar
  16. Parkin DM, Bray F, Ferlay J, Pisani P (2001) Estimating the world cancer burden: globocan 2000. Int J Cancer 94:153–156PubMedCrossRefGoogle Scholar
  17. Song LB, Zeng MS, Liao WT, Zhang L, Mo HY, Liu WL, Shao JY, Wu QL, Li MZ, Xia YF, Fu LW, Huang WL, Dimri GP, Band V, Zeng YX (2006) Bmi-1 is a novel molecular marker of nasopharyngeal carcinoma progression and immortalizes primary human nasopharyngeal epithelial cells. Cancer Res 66:6225–6232PubMedCrossRefGoogle Scholar
  18. Steele JC, Torr EE, Noakes KL, Kalk E, Moss PA, Reynolds GM, Hubscher SG, van Lohuizen M, Adams DH, Young LS (2006) The polycomb group proteins, BMI-1 and EZH2, are tumour-associated antigens. Br J Cancer 95:1202–1211PubMedCrossRefGoogle Scholar
  19. Tateishi K, Ohta M, Kanai F, Guleng B, Tanaka Y, Asaoka Y, Tada M, Seto M, Jazag A, Lianjie L, Okamoto M, Isayama H, Tada M, Yoshida H, Kawabe T, Omata M (2006) Dysregulated expression of stem cell factor Bmi-1 in precancerous lesions of the gastrointestinal tract. Clin Cancer Res 12:6960–6966PubMedCrossRefGoogle Scholar
  20. Thomas MB, Zhu AX (2005) Hepatocellular carcinoma: the need for progress. J Clin Oncol 23:2892–2899PubMedCrossRefGoogle Scholar
  21. van Galen JC, Muris JJ, Oudejans JJ, Vos W, Giroth CP, Ossenkoppele GJ, Otte AP, Raaphorst FM, Meijer CJ (2007) Expression of the polycomb-group gene Bmi-1 is related to an unfavourable prognosis in primary nodal DLBCL. J Clin Pathol 60:167–172PubMedCrossRefGoogle Scholar
  22. van Leenders GJ, Dukers D, Hessels D, van den Kieboom SW, Hulsbergen CA, Witjes JA, Otte AP, Meijer CJ, Raaphorst FM (2007) Polycomb-group oncogenes EZH2, Bmi-1, and RING1 are overexpressed in prostate cancer with adverse pathologic and clinical features. Eur Urol 52:455–463PubMedCrossRefGoogle Scholar
  23. van Lohuizen M, Frasch M, Wientjens E, Berns A (1991) Sequence similarity between the mammalian bmi-1 proto-oncogene and the Drosophila regulatory genes Psc and Su(z)2. Nature 353:353–355PubMedCrossRefGoogle Scholar
  24. Vonlanthen S, Heighway J, Altermatt HJ, Gugger M, Kappeler A, Borner MM, van Lohuizen M, Betticher DC (2001) The bmi-1 oncoprotein is differentially expressed in non-small cell lung cancer and correlates with INK4A-ARF locus expression. Br J Cancer 84:1372–1376PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Hui Wang
    • 1
  • Ke Pan
    • 1
  • Hua-kun Zhang
    • 1
  • De-sheng Weng
    • 1
  • Jun Zhou
    • 1
  • Jian-jun Li
    • 1
  • Wei Huang
    • 1
  • Hai-feng Song
    • 1
  • Min-shan Chen
    • 2
  • Jian-chuan Xia
    • 1
    Email author
  1. 1.State Key Laboratory of Oncology in Southern China and Department of Experimental ResearchSun Yat-sen University Cancer CenterGuangzhouPeople’s Republic of China
  2. 2.Department of Hepatobilary OncologySun Yat-sen University Cancer CenterGuangzhouPeople’s Republic of China

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